Exploration of Drug Science

Table 4. Summary of tumour necrosis factor (TNF) ligands. TNF ligands are presented in literature but not discussed in this review

Compound	Cancer type	Clinical trials	References
Tetrandrine	Prostate cancer	-	[170]
Tannic acid	Embryonic carcinoma	-	[171]
Scutellarein	Hepatocellular carcinoma	-	[172]
CPT211	Triple negative breast cancer	-	[173]
Apigetrin	Gastric cancer	-	[174]
Gentian violet	Cutaneous T-cell lymphoma	-	[175]
Compound 3	Non-small cell lung cancer	-	[176]
Pemetrexed^※	Non-small cell lung cancer	NCT01769066	[177]
ASTX660^※	Head and neck squamous cell carcinomas	NCT05245682	[178]
Ruthenium complex 2c	Melanoma; breast cancer, lung cancer	-	[179]
Mn^III complex	Triple negative breast cancer	-	[180]
Erinacine A	Colorectal cancer	-	[181]
C20E	Triple negative breast cancer	-	[182]
1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP)	Melanoma	-	[183]
Licochalcone B	Melanoma, squamous cell carcinoma	-	[184]
Erinacine S	Gastric cancer	-	[185]
Cedrol	Glioblastoma	-	[186]
3β-Acetyl-nor-erythrophlamide (C5)	Lung cancer, lymphoma	-	[174]
Demethylzeylasteral (T-96)	Prostate cancer	-	[187]

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^※ Drugs in clinical trial for different cancer types; -: no data

Declarations

Author contributions

AV and RDM: Conceptualization, Validation, Writing—original draft, Writing—review & editing, Supervision. DL: Validation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019;20:175–93. [DOI] [PubMed] [PMC]

Vitale I, Pietrocola F, Guilbaud E, Aaronson SA, Abrams JM, Adam D, et al. Apoptotic cell death in disease—Current understanding of the NCCD 2023. Cell Death Differ. 2023;30:1097–154. [DOI] [PubMed] [PMC]

Cavalcante GC, Schaan AP, Cabral GF, Santana-da-Silva MN, Pinto P, Vidal AF, et al. A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis. Int J Mol Sci. 2019;20:4133. [DOI] [PubMed] [PMC]

8D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43:582–92. [DOI] [PubMed]

Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29:347–64. [DOI] [PubMed] [PMC]

Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002;2:183–92. [DOI] [PubMed]

Corazzari M, Gagliardi M, Fimia GM, Piacentini M. Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate. Front Oncol. 2017;7:78. [DOI] [PubMed] [PMC]

De Zio D, Cianfanelli V, Cecconi F. New insights into the link between DNA damage and apoptosis. Antioxid Redox Signal. 2013;19:559–71. [DOI] [PubMed] [PMC]

Klein JA, Ackerman SL. Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest. 2003;111:785–93. [DOI] [PubMed] [PMC]

10.

Letai A. Growth factor withdrawal and apoptosis: the middle game. Mol Cell. 2006;21:728–30. [DOI] [PubMed]

11.

Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review. Anticancer Res. 2020;40:6009–15. [DOI] [PubMed]

12.

McMahon SB. MYC and the control of apoptosis. Cold Spring Harb Perspect Med. 2014;4:a014407. [DOI] [PubMed] [PMC]

13.

Shortt J, Johnstone RW. Oncogenes in cell survival and cell death. Cold Spring Harb Perspect Biol. 2012;4:a009829. [DOI] [PubMed] [PMC]

14.

Maas C, Verbrugge I, de Vries E, Savich G, van de Kooij LW, Tait SW, et al. Smac/DIABLO release from mitochondria and XIAP inhibition are essential to limit clonogenicity of Type I tumor cells after TRAIL receptor stimulation. ell Death Differ. 2010;17:1613–23. [DOI] [PubMed]

15.

Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol. 2022;12:985363. [DOI] [PubMed] [PMC]

16.

Brunet CL, Gunby RH, Benson RS, Hickman JA, Watson AJ, Brady G. Commitment to cell death measured by loss of clonogenicity is separable from the appearance of apoptotic markers. Cell Death Differ. 1998;5:107–15. [DOI] [PubMed]

17.

Marsden VS, O’Connor L, O’Reilly LA, Silke J, Metcalf D, Ekert PG, et al. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature. 2002;419:634–7. [DOI] [PubMed]

18.

Tait SWG, Green DR. Mitochondrial regulation of cell death. Cold Spring Harb Perspect Biol. 2013;5:a008706. [DOI] [PubMed] [PMC]

19.

Birkinshaw RW, Czabotar PE. The BCL-2 family of proteins and mitochondrial outer membrane permeabilisation. Semin Cell Dev Biol. 2017;72:152–62. [DOI] [PubMed]

20.

Wang S, Martin SM, Harris PS, Knudson CM. Caspase inhibition blocks cell death and enhances mitophagy but fails to promote T-cell lymphoma. PLoS One. 2011;6:e19786. [DOI] [PubMed] [PMC]

21.

Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486–541. [DOI] [PubMed] [PMC]

22.

Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012;19:107–20. [DOI] [PubMed] [PMC]

23.

Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol. 2013;5:a008672. [DOI] [PubMed] [PMC]

24.

Shamas-Din A, Brahmbhatt H, Leber B, Andrews DW. BH3-only proteins: Orchestrators of apoptosis. Biochim Biophys Acta. 2011;1813:508–20. [DOI] [PubMed]

25.

Vo TT, Letai A. BH3-only proteins and their effects on cancer. Adv Exp Med Biol. 2010;687:49–63. [DOI] [PubMed] [PMC]

26.

Diepstraten ST, Anderson MA, Czabotar PE, Lessene G, Strasser A, Kelly GL. The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs. Nat Rev Cancer. 2022;22:45–64. [DOI] [PubMed]

27.

Montero J, Haq R. Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics. Cancer Discov. 2022;12:1217–32. [DOI] [PubMed] [PMC]

28.

Sharma A, Boise LH, Shanmugam M. Cancer Metabolism and the Evasion of Apoptotic Cell Death. Cancers (Basel). 2019;11:1144. [DOI] [PubMed] [PMC]

29.

Jäger R, Herzer U, Schenkel J, Weiher H. Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice. Oncogene. 1997;15:1787–95. [DOI] [PubMed]

30.

Jamerson MH, Johnson MD, Korsmeyer SJ, Furth PA, Dickson RB. Bax regulates c-Myc-induced mammary tumour apoptosis but not proliferation in MMTV-c-myc transgenic mice. Br J Cancer. 2004;91:1372–9. [DOI] [PubMed] [PMC]

31.

Bean GR, Ganesan YT, Dong Y, Takeda S, Liu H, Chan PM, et al. PUMA and BIM are required for oncogene inactivation–induced apoptosis. Sci Signal. 2013;6:ra20. [DOI] [PubMed] [PMC]

32.

Parsons MJ, McCormick L, Janke L, Howard A, Bouchier-Hayes L, Green DR. Genetic deletion of caspase-2 accelerates MMTV/c-neu-driven mammary carcinogenesis in mice. Cell Death Differ. 2013;20:1174–82. [DOI] [PubMed] [PMC]

33.

Qiu W, Carson-Walter EB, Kuan SF, Zhang L, Yu J. PUMA suppresses intestinal tumorigenesis in mice. Cancer Res. 2009;69:4999–5006. [DOI] [PubMed] [PMC]

34.

Colak S, Zimberlin CD, Fessler E, Hogdal L, Prasetyanti PR, Grandela CM, et al. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. 2014;21:1170–7. [DOI] [PubMed] [PMC]

35.

Zeuner A, Francescangeli F, Contavalli P, Zapparelli G, Apuzzo T, Eramo A, et al. Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-X_L inhibition in non-small cell lung cancer. Cell Death Differ. 2014;21:1877–88. [DOI] [PubMed] [PMC]

36.

Delbridge AR, Grabow S, Strasser A, Vaux DL. Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. Nat Rev Cancer. 2016;16:99–109. [DOI] [PubMed]

37.

Perini GF, Ribeiro GN, Pinto Neto JV, Campos LT, Hamerschlak N. BCL-2 as therapeutic target for hematological malignancies. J Hematol Oncol. 2018;11:65. [DOI] [PubMed] [PMC]

38.

Högstrand K, Hejll E, Sander B, Rozell B, Larsson LG, Grandien A. Inhibition of the intrinsic but not the extrinsic apoptosis pathway accelerates and drives MYC-driven tumorigenesis towards acute myeloid leukemia. PLoS One. 2012;7:e31366. [DOI] [PubMed] [PMC]

39.

Eischen CM, Roussel MF, Korsmeyer SJ, Cleveland JL. Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol. 2001;21:7653–62. [DOI] [PubMed] [PMC]

40.

Egle A, Harris AW, Bouillet P, Cory S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci U S A. 2004;101:6164–9. [DOI] [PubMed] [PMC]

41.

Delbridge AR, Grabow S, Bouillet P, Adams JM, Strasser A. Functional antagonism between pro-apoptotic BIM and anti-apoptotic BCL-XL in MYC-induced lymphomagenesis. Oncogene. 2015;34:1872–6. [DOI] [PubMed]

42.

Frenzel A, Labi V, Chmelewskij W, Ploner C, Geley S, Fiegl H, et al. Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad. Blood. 2010;115:995–1005. [DOI] [PubMed] [PMC]

43.

Hemann MT, Zilfou JT, Zhao Z, Burgess DJ, Hannon GJ, Lowe SW. Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci U S A. 2004;101:9333–8. [DOI] [PubMed] [PMC]

44.

Shang Q, Zhang D, Guo C, Lin Q, Guo Z, Deng C. Potential synergism of Bim with p53 in mice with Mycinduced lymphoma in a mouse lymphoma model. Mol Med Rep. 2012;5:1401–8. [DOI] [PubMed]

45.

Ku B, Liang C, Jung JU, Oh BH. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res. 2011;21:627–41. [DOI] [PubMed] [PMC]

46.

Birkinshaw RW, Gong JN, Luo CS, Lio D, White CA, Anderson MA, et al. Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Nat Commun. 2019;10:2385. [DOI] [PubMed] [PMC]

47.

Sehnal D, Bittrich S, Deshpande M, Svobodová R, Berka K, Bazgier V, et al. Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures. Nucleic Acids Res. 2021;49:W431–7. [DOI] [PubMed] [PMC]

48.

Zhang P, Luo W, Zhang Z, Lv M, Sang L, Wen Y, et al. A Lipid-Sensitive Spider Peptide Toxin Exhibits Selective Anti-Leukemia Efficacy through Multimodal Mechanisms. Adv Sci (Weinh). 2024;11:e2404937. [DOI] [PubMed] [PMC]

49.

Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016;8:603–19. [DOI] [PubMed] [PMC]

50.

Kaloni D, Diepstraten ST, Strasser A, Kelly GL. BCL-2 protein family: attractive targets for cancer therapy. Apoptosis. 2023;28:20–38. [DOI] [PubMed] [PMC]

51.

Kotschy A, Szlavik Z, Murray J, Davidson J, Maragno AL, Le Toumelin-Braizat G, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016;538:477–482. [DOI] [PubMed]

52.

Caenepeel S, Brown SP, Belmontes B, Moody G, Keegan KS, Chui D, et al. AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. Cancer Discov. 2018;8:1582–97. [DOI] [PubMed]

53.

Sejic N, George LC, Tierney RJ, Chang C, Kondrashova O, MacKinnon RN, et al. BCL-XL inhibition by BH3-mimetic drugs induces apoptosis in models of Epstein-Barr virus–associated T/NK-cell lymphoma. Blood Adv. 2020;4:4775–87. [DOI] [PubMed] [PMC]

54.

Adams CM, Mitra R, Vogel AN, Liu J, Gong JZ, Eischen CM. Targeting BCL-W and BCL-XL as a therapeutic strategy for Hodgkin lymphoma. Leukemia. 2020;34:947–52. [DOI] [PubMed] [PMC]

55.

Vogler M, Hamali HA, Sun XM, Bampton ET, Dinsdale D, Snowden RT, et al. BCL2/BCL-X_L inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood. 2011;117:7145–54. [DOI] [PubMed]

56.

Al-Harbi S, Hill BT, Mazumder S, Singh K, Devecchio J, Choudhary G, et al. An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737. Blood. 2011;118:3579–90. [DOI] [PubMed] [PMC]

57.

Bierbrauer A, Jacob M, Vogler M, Fulda S. A direct comparison of selective BH3-mimetics reveals BCL-X_L, BCL-2 and MCL-1 as promising therapeutic targets in neuroblastoma. Br J Cancer. 2020;122:1544–51. [DOI] [PubMed] [PMC]

58.

Pan RA, Wang Y, Qiu S, Villalobos-Ortiz M, Ryan J, Morris E, et al. BH3 profiling as pharmacodynamic biomarker for the activity of BH3 mimetics. Haematologica. 2024;109:1253–8. [DOI] [PubMed] [PMC]

59.

Deeks ED. Venetoclax: First Global Approval. Drugs. 2016;76:979–87. [DOI] [PubMed]

60.

Wang CW, Chen J, inventor. N-(phenylsulfonyl)benzamides and Related Compounds as Bcl-2 Inhibitors. WIPO (PCT) patent WO 2018027097. 2018 Feb 8.

61.

Le Diguarher T, Casara P, Starck JB, Henlin JM, Davidson JEP, Murray JB, inventor; Servier Lab., assignee. Vernalis R & D Ltd., assignee. New Indolizine Derivatives, Method for Preparing Same and Pharmaceutical Compositions Containing Same. WIPO (PCT) patent WO 2013110890. 2013 Aug 1.

62.

Tao ZF, Hasvold L, Wang L, Wang X, Petros AM, Park CH, et al. Discovery of a Potent and Selective BCL-X_L Inhibitor with in Vivo Activity. ACS Med Chem Lett. 2014;5:1088–93. [DOI] [PubMed] [PMC]

63.

Wang L, Doherty GA, Judd AS, Tao ZF, Hansen TM, Frey RR, et al. Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-X_L Inhibitor. ACS Med Chem Lett. 2020;11:1829–36. [DOI] [PubMed] [PMC]

64.

Lessene G, Czabotar PE, Sleebs BE, Zobel K, Lowes KN, Adams JM, et al. Structure-guided design of a selective BCL-X_L inhibitor. Nat Chem Biol. 2013;9:390–7. [DOI] [PubMed]

65.

Park CM, Bruncko M, Adickes J, Bauch J, Ding H, Kunzer A, et al. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins. J Med Chem. 2008;51:6902–15. [DOI] [PubMed]

66.

Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68:3421–8. [DOI] [PubMed]

67.

Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677–81. [DOI] [PubMed]

68.

Szlavik Z, Csekei M, Paczal A, Szabo ZB, Sipos S, Radics G, et al. Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor. J Med Chem. 2020;63:13762–95. [DOI] [PubMed]

69.

Szlávik Z, Ondi L, Csékei M, Paczal A, Szabó ZB, Radics G, et al. Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity. J Med Chem. 2019;62:6913–24. [DOI] [PubMed]

70.

Pelz NF, Bian Z, Zhao B, Shaw S, Tarr JC, Belmar J, et al. Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods. J Med Chem. 2016;59:2054–66. [DOI] [PubMed] [PMC]

71.

Shaw S, Bian Z, Zhao B, Tarr JC, Veerasamy N, Jeon KO, et al. Optimization of Potent and Selective Tricyclic Indole Diazepinone Myeloid Cell Leukemia-1 Inhibitors Using Structure-Based Design. J Med Chem. 2018;61:2410–21. [DOI] [PubMed]

72.

Tron AE, Belmonte MA, Adam A, Aquila BM, Boise LH, Chiarparin E, et al. Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. Nat Commun. 2018;9:5341. [DOI] [PubMed] [PMC]

73.

Brown SP, Li Y, Lizarzaburu ME, Lucas BS, Paras NA, Taygerly J, inventor; Amgen Inc., assignee. Tetrahydronaphthalene Derivatives That Inhibit Mcl-1 Protein. WIPO (PCT) patent WO 2016033486. 2016 Mar 3.

74.

Wang S, Wang G, Tang G, Wang R, Nikolovska-Coleska Z, Yang D, inventor; University of Michigan, assignee. Small molecule inhibitors of anti-apoptotic BCL-2 family members and the uses thereof. United States patent US 20060084647. 2013 Oct 15.

75.

Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19:202–8. [DOI] [PubMed]

76.

Ryan CE, Davids MS. BCL-2 Inhibitors, Present and Future. Cancer J. 2019;25:401–9. [DOI] [PubMed]

77.

Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374:311–22. [DOI] [PubMed] [PMC]

78.

Montero J, Stephansky J, Cai T, Griffin GK, Cabal-Hierro L, Togami K, et al. Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax. Cancer Discov. 2017;7:156–64. [DOI] [PubMed] [PMC]

79.

Alcon C, Manzano-Muñoz A, Prada E, Mora J, Soriano A, Guillén G, et al. Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance. Cell Death Dis. 2020;11:634. [DOI] [PubMed] [PMC]

80.

Beltrán-Visiedo M, Jiménez-Alduán N, Díez R, Cuenca M, Benedi A, Serrano-Del Valle A, et al. Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-X_L in multiple myeloma cell lines partially dependent on MCL-1 and in plasma cells from patients. Mol Oncol. 2023;17:2507–25. [DOI] [PubMed] [PMC]

81.

Iacovelli S, Ricciardi MR, Allegretti M, Mirabilii S, Licchetta R, Bergamo P, et al. Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia. Oncotarget. 2015;6:32089–103. [DOI] [PubMed] [PMC]

82.

Zall H, Weber A, Besch R, Zantl N, Häcker G. Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1. Mol Cancer. 2010;9:164. [DOI] [PubMed] [PMC]

83.

Zhu R, Li L, Nguyen B, Seo J, Wu M, Seale T, et al. FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation. Signal Transduct Target Ther. 2021;6:186. [DOI] [PubMed] [PMC]

84.

Bodo J, Zhao X, Durkin L, Souers AJ, Phillips DC, Smith MR, et al. Acquired resistance to venetoclax (ABT-199) in t(14;18) positive lymphoma cells. Oncotarget. 2016;7:70000–10. [DOI] [PubMed] [PMC]

85.

Tausch E, Close W, Dolnik A, Bloehdorn J, Chyla B, Bullinger L, et al. Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia. Haematologica. 2019;104:e434–7. [DOI] [PubMed] [PMC]

86.

Klener P, Sovilj D, Renesova N, Andera L. BH3 Mimetics in Hematologic Malignancies. Int J Mol Sci. 2021;22:10157. [DOI] [PubMed] [PMC]

87.

Cragg MS, Harris C, Strasser A, Scott CL. Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer. 2009;9:321–6. [DOI] [PubMed]

88.

Gross S, Rahal R, Stransky N, Lengauer C, Hoeflich KP. Targeting cancer with kinase inhibitors. J Clin Invest. 2015;125:1780–9. [DOI] [PubMed] [PMC]

89.

Turdo A, D’Accardo C, Glaviano A, Porcelli G, Colarossi C, Colarossi L, et al. Targeting Phosphatases and Kinases: How to Checkmate Cancer. Front Cell Dev Biol. 2021;9:690306. [DOI] [PubMed] [PMC]

90.

Riegel K, Vijayarangakannan P, Kechagioglou P, Bogucka K, Rajalingam K. Recent advances in targeting protein kinases and pseudokinases in cancer biology. Front Cell Dev Biol. 2022;10:942500. [DOI] [PubMed] [PMC]

91.

Lee PY, Yeoh Y, Low TY. A recent update on small-molecule kinase inhibitors for targeted cancer therapy and their therapeutic insights from mass spectrometry-based proteomic analysis. FEBS J. 2023;290:2845–64. [DOI] [PubMed]

92.

Montero J, Gstalder C, Kim DJ, Sadowicz D, Miles W, Manos M, et al. Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies. Nat Commun. 2019;10:5157. [DOI] [PubMed] [PMC]

93.

Valentini E, Di Martile M, Brignone M, Di Caprio M, Manni I, Chiappa M, et al. Bcl-2 family inhibitors sensitize human cancer models to therapy. Cell Death Dis. 2023;14:441. [DOI] [PubMed] [PMC]

94.

Nangia V, Siddiqui FM, Caenepeel S, Timonina D, Bilton SJ, Phan N, et al. Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS-Mutant Non-Small Cell Lung Cancer. Cancer Discov. 2018;8:1598–613. [DOI] [PubMed] [PMC]

95.

Cragg MS, Jansen ES, Cook M, Harris C, Strasser A, Scott CL. Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J Clin Invest. 2008;118:3651–9. [DOI] [PubMed] [PMC]

96.

Sale MJ, Cook SJ. The BH3 mimetic ABT-263 synergizes with the MEK1/2 inhibitor selumetinib/AZD6244 to promote BIM-dependent tumour cell death and inhibit acquired resistance. Biochem J. 2013;450:285–94. [DOI] [PubMed]

97.

Verhaegen M, Bauer JA, Martín de la Vega C, Wang G, Wolter KG, Brenner JC, et al. A novel BH3 mimetic reveals a mitogen-activated protein kinase–dependent mechanism of melanoma cell death controlled by p53 and reactive oxygen species. Cancer Res. 2006;66:11348–59. [DOI] [PubMed]

98.

Bhullar KS, Lagarón NO, McGowan EM, Parmar I, Jha A, Hubbard BP, et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer. 2018;17:48. [DOI] [PubMed] [PMC]

99.

Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell. 2018;173:321–37.e10. [DOI] [PubMed] [PMC]

100.

Venerando A, Ruzzene M, Pinna LA. Casein kinase: the triple meaning of a misnomer. Biochem J. 2014;460:141–56. [DOI] [PubMed]

101.

Halloran D, Pandit V, Nohe A. The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review. J Dev Biol. 2022;10:31. [DOI] [PubMed] [PMC]

102.

Meggio F, Pinna LA. One-thousand-and-one substrates of protein kinase CK2? FASEB J. 2003;17:349–68. [DOI] [PubMed]

103.

Venerando A, Cesaro L, Pinna LA. From phosphoproteins to phosphoproteomes: a historical account. FEBS J. 2017;284:1936–51. [DOI] [PubMed]

104.

Borgo C, Ruzzene M. Role of protein kinase CK2 in antitumor drug resistance. J Exp Clin Cancer Res. 2019;38:287. [DOI] [PubMed] [PMC]

105.

Strum SW, Gyenis L, Litchfield DW. CSNK2 in cancer: pathophysiology and translational applications. Br J Cancer. 2022;126:994–1003. [DOI] [PubMed] [PMC]

106.

Manni S, Pesavento M, Spinello Z, Saggin L, Arjomand A, Fregnani A, et al. Protein Kinase CK2 represents a new target to boost Ibrutinib and Venetoclax induced cytotoxicity in mantle cell lymphoma. Front Cell Dev Biol. 2022;10:935023. [DOI] [PubMed] [PMC]

107.

Borgo C, D’Amore C, Sarno S, Salvi M, Ruzzene M. Protein kinase CK2: a potential therapeutic target for diverse human diseases. Signal Transduct Target Ther. 2021;6:183. [DOI] [PubMed] [PMC]

108.

Siddiqui-Jain A, Drygin D, Streiner N, Chua P, Pierre F, O’Brien SE, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010;70:10288–98. [DOI] [PubMed]

109.

Zanin S, Molinari S, Cozza G, Magro M, Fedele G, Vianello F, et al. Intracellular protein kinase CK2 inhibition by ferulic acid-based trimodal nanodevice. Int J Biol Macromol. 2020;165:701–12. [DOI] [PubMed]

110.

Fasolato L, Magro M, Cozza G, Sbarra F, Molinari S, Novelli E, et al. An Iron Shield to Protect Epigallocatehin-3-Gallate from Degradation: Multifunctional Self-Assembled Iron Oxide Nanocarrier Enhances Protein Kinase CK2 Intracellular Targeting and Inhibition. Pharmaceutics. 2021;13:1266. [DOI] [PubMed] [PMC]

111.

Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c–dependent caspase activation by eliminating IAP inhibition. Cell. 2000;102:33–42. [DOI] [PubMed]

112.

Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000;102:43–53. [DOI] [PubMed]

113.

Chen DJ, Huerta S. Smac mimetics as new cancer therapeutics. Anticancer Drugs. 2009;20:646–58. [DOI] [PubMed]

114.

Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature. 2000;408:1008–12. [DOI] [PubMed]

115.

Liu Z, Sun C, Olejniczak ET, Meadows RP, Betz SF, Oost T, et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature. 2000;408:1004–8. [DOI] [PubMed]

116.

Wist AD, Gu L, Riedl SJ, Shi Y, McLendon GL. Structure–activity based study of the Smac-binding pocket within the BIR3 domain of XIAP. Bioorg Med Chem. 2007;15:2935–43. [DOI] [PubMed]

117.

Oost TK, Sun C, Armstrong RC, Al-Assaad AS, Betz SF, Deckwerth TL, et al. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem. 2004;47:4417–26. [DOI] [PubMed]

118.

Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, et al. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 2012;55:4101–13. [DOI] [PubMed] [PMC]

119.

Wong H, Gould SE, Budha N, Darbonne WC, Kadel EE 3rd, La H, et al. Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos. 2013;41:2104–13. [DOI] [PubMed]

120.

Chang YC, Kondapuram SK, Yang TH, Syed SB, Cheng SM, Lin TY, et al. The SMAC mimetic LCL161 is a direct ABCB1/MDR1-ATPase activity modulator and BIRC5/Survivin expression down-regulator in cancer cells. Toxicol Appl Pharmacol. 2020;401:115080. [DOI] [PubMed]

121.

Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, et al. A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem. 2011;54:2714–26. [DOI] [PubMed] [PMC]

122.

Weisberg E, Ray A, Barrett R, Nelson E, Christie AL, Porter D, et al. Smac mimetics: implications for enhancement of targeted therapies in leukemia. Leukemia. 2010;24:2100–9. [DOI] [PubMed] [PMC]

123.

Fulda S. Promises and Challenges of Smac Mimetics as Cancer Therapeutics. Clin Cancer Res. 2015;21:5030–6. [DOI] [PubMed]

124.

Bai L, Smith DC, Wang S. Small-molecule SMAC mimetics as new cancer therapeutics. Pharmacol Ther. 2014;144:82–95. [DOI] [PubMed] [PMC]

125.

Hu R, Li J, Liu Z, Miao M, Yao K. GDC-0152 induces apoptosis through down-regulation of IAPs in human leukemia cells and inhibition of PI3K/Akt signaling pathway. Tumour Biol. 2015;36:577–84. [DOI] [PubMed]

126.

Shekhar TM, Burvenich IJG, Harris MA, Rigopoulos A, Zanker D, Spurling A, et al. Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice. BMC Cancer. 2019;19:924. [DOI] [PubMed] [PMC]

127.

Tchoghandjian A, Soubéran A, Tabouret E, Colin C, Denicolaï E, Jiguet-Jiglaire C, et al. Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152. Cell Death Dis. 2016;7:e2325. [DOI] [PubMed] [PMC]

128.

Chang YC, Cheung CHA. An updated review of smac mimetics, LCL161, birinapant, and GDC-0152 in cancer treatment. Appl Sci. 2020;11:335. [DOI]

129.

Chauhan D, Neri P, Velankar M, Podar K, Hideshima T, Fulciniti M, et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood. 2007;109:1220–7. [DOI] [PubMed] [PMC]

130.

Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell. 2007;131:669–81. [DOI] [PubMed]

131.

Ndubaku C, Varfolomeev E, Wang L, Zobel K, Lau K, Elliott LO, et al. Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists. ACS Chem Biol. 2009;4:557–66. [DOI] [PubMed]

132.

Bourguet CB, Boulay PL, Claing A, Lubell WD. Design and synthesis of novel azapeptide activators of apoptosis mediated by caspase-9 in cancer cells. Bioorg Med Chem Lett. 2014;24:3361–5. [DOI] [PubMed]

133.

Cossu F, Milani M, Mastrangelo E, Vachette P, Servida F, Lecis D, et al. Structural basis for bivalent Smac-mimetics recognition in the IAP protein family. J Mol Biol. 2009;392:630–44. [DOI] [PubMed]

134.

Corti A, Milani M, Lecis D, Seneci P, de Rosa M, Mastrangelo E, et al. Structure-based design and molecular profiling of Smac-mimetics selective for cellular IAPs. FEBS J. 2018;285:3286–98. [DOI] [PubMed]

135.

Benetatos CA, Mitsuuchi Y, Burns JM, Neiman EM, Condon SM, Yu G, et al. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models. Mol Cancer Ther. 2014;13:867–79. [DOI] [PubMed]

136.

Damgaard RB, Fiil BK, Speckmann C, Yabal M, zur Stadt U, Bekker-Jensen S, et al. Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling. EMBO Mol Med. 2013;5:1278–95. [DOI] [PubMed] [PMC]

137.

Amaravadi RK, Schilder RJ, Martin LP, Levin M, Graham MA, Weng DE, et al. A Phase I Study of the SMAC-Mimetic Birinapant in Adults with Refractory Solid Tumors or Lymphoma. Mol Cancer Ther. 2015;14:2569–75. [DOI] [PubMed]

138.

Condon SM, Mitsuuchi Y, Deng Y, LaPorte MG, Rippin SR, Haimowitz T, et al. Birinapant, a smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. J Med Chem. 2014;57:3666–77. [DOI] [PubMed]

139.

Amaravadi RK, Schilder RJ, Dy GK, Ma WW, Fetterly GJ, Weng DE, et al. Abstract LB-406: Phase 1 study of the Smac mimetic TL32711 in adult subjects with advanced solid tumors and lymphoma to evaluate safety, pharmacokinetics, pharmacodynamics, and antitumor activity. Cancer Res. 2011;71:LB-406. [DOI]

140.

Li N, Feng L, Han HQ, Yuan J, Qi XK, Lian YF, et al. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis. Cancer Lett. 2016;381:14–22. [DOI] [PubMed]

141.

Cossu F, Milani M, Vachette P, Malvezzi F, Grassi S, Lecis D, et al. Structural insight into inhibitor of apoptosis proteins recognition by a potent divalent smac-mimetic. PLoS One. 2012;7:e49527. [DOI] [PubMed] [PMC]

142.

Fischer K, Tognarelli S, Roesler S, Boedicker C, Schubert R, Steinle A, et al. The Smac Mimetic BV6 Improves NK Cell-Mediated Killing of Rhabdomyosarcoma Cells by Simultaneously Targeting Tumor and Effector Cells. Front Immunol. 2017;8:202. [DOI] [PubMed] [PMC]

143.

Sun H, Nikolovska-Coleska Z, Yang CY, Qian D, Lu J, Qiu S, et al. Design of small-molecule peptidic and nonpeptidic Smac mimetics. Acc Chem Res. 2008;41:1264–77. [DOI] [PubMed] [PMC]

144.

Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700. [DOI] [PubMed]

145.

Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, et al. IAP antagonists target cIAP1 to induce TNFα-dependent apoptosis. Cell. 2007;131:682–93. [DOI] [PubMed]

146.

Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG. A small molecule Smac mimic potentiates TRAIL- and TNFα-mediated cell death. Science. 2004;305:1471–4. [DOI] [PubMed]

147.

Micewicz ED, Luong HT, Jung CL, Waring AJ, McBride WH, Ruchala P. Novel dimeric Smac analogs as prospective anticancer agents. Bioorg Med Chem Lett. 2014;24:1452–7. [DOI] [PubMed]

148.

Lecis D, Mastrangelo E, Belvisi L, Bolognesi M, Civera M, Cossu F, et al. Dimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part II: Structural and biological characterization. Bioorg Med Chem. 2012;20:6709–23. [DOI] [PubMed]

149.

Gentilucci L, De Marco R, Cerisoli L. Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr Pharm Des. 2010;16:3185–203. [DOI] [PubMed]

150.

Hossbach J, Michalsky E, Henklein P, Jaeger M, Daniel PT, Preissner R. Inhibiting the inhibitors: retro-inverso Smac peptides. Peptides. 2009;30:2374–9. [DOI] [PubMed]

151.

Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3:16–20. [DOI] [PubMed]

152.

Li M, Liu P, Gao G, Deng J, Pan Z, Wu X, et al. Smac therapeutic Peptide nanoparticles inducing apoptosis of cancer cells for combination chemotherapy with Doxorubicin. ACS Appl Mater Interfaces. 2015;7:8005–12. [DOI] [PubMed]

153.

De Marco R, Rampazzo E, Zhao J, Prodi L, Paolillo M, Picchetti P, et al. Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein. Nanomaterials (Basel). 2020;10:1211. [DOI] [PubMed] [PMC]

154.

De Marco R, Tolomelli A, Juaristi E, Gentilucci L. Integrin Ligands with α/β-Hybrid Peptide Structure: Design, Bioactivity, and Conformational Aspects. Med Res Rev. 2016;36:389–424. [DOI] [PubMed]

155.

Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22. [DOI] [PubMed] [PMC]

156.

Di Giorgio E, Ferino A, Huang W, Simonetti S, Xodo L, De Marco R. Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells. Front Pharmacol. 2023;14:1237478. [DOI] [PubMed] [PMC]

157.

Nejabat M, Eisvand F, Soltani F, Alibolandi M, Mohammad Taghdisi S, Abnous K, et al. Combination therapy using Smac peptide and doxorubicin-encapsulated MUC 1-targeted polymeric nanoparticles to sensitize cancer cells to chemotherapy: An in vitro and in vivo study. Int J Pharm. 2020;587:119650. [DOI] [PubMed]

158.

Nikkhoo A, Rostami N, Farhadi S, Esmaily M, Moghadaszadeh Ardebili S, Atyabi F, et al. Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell progression. Int J Pharm. 2020;581:119236. [DOI] [PubMed]

159.

Jadidi-Niaragh F, Atyabi F, Rastegari A, Kheshtchin N, Arab S, Hassannia H, et al. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice. J Control Release. 2017;246:46–59. [DOI] [PubMed]

160.

Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 2020;17:395–417. [DOI] [PubMed] [PMC]

161.

Hsieh SL, Lin WW. Decoy receptor 3: an endogenous immunomodulator in cancer growth and inflammatory reactions. J Biomed Sci. 2017;24:39. [DOI] [PubMed] [PMC]

162.

Kostova I, Mandal R, Becker S, Strebhardt K. The role of caspase-8 in the tumor microenvironment of ovarian cancer. Cancer Metastasis Rev. 2021;40:303–18. [DOI] [PubMed] [PMC]

163.

Zhang L, Zhu H, Teraishi F, Davis JJ, Guo W, Fan Z, et al. Accelerated degradation of caspase-8 protein correlates with TRAIL resistance in a DLD1 human colon cancer cell line. Neoplasia. 2005;7:594–602. [DOI] [PubMed] [PMC]

164.

Peng F, Liao M, Qin R, Zhu S, Peng C, Fu L, et al. Regulated cell death (RCD) in cancer: key pathways and targeted therapies. Signal Transduct Target Ther. 2022;7:286. [DOI] [PubMed] [PMC]

165.

Kline CL, Van den Heuvel AP, Allen JE, Prabhu VV, Dicker DT, El-Deiry WS. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases. Sci Signal. 2016;9:ra18. [DOI] [PubMed] [PMC]

166.

Hsu FT, Chiang IT, Wang WS. Induction of apoptosis through extrinsic/intrinsic pathways and suppression of ERK/NF-κB signalling participate in anti-glioblastoma of imipramine. J Cell Mol Med. 2020;24:3982–4000. [DOI] [PubMed] [PMC]

167.

Smith HG, Cartwright J, Wilkinson MJ, Strauss DC, Thomas JM, Hayes AJ. Isolated Limb Perfusion with Melphalan and Tumour Necrosis Factor α for In-Transit Melanoma and Soft Tissue Sarcoma. Ann Surg Oncol. 2015;22:S356–61. [DOI] [PubMed]

168.

Deng D, Shah K. TRAIL of Hope Meeting Resistance in Cancer. Trends Cancer. 2020;6:989–1001. [DOI] [PubMed] [PMC]

169.

Wagner J, Kline CL, Pottorf RS, Nallaganchu BR, Olson GL, Dicker DT, et al. The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity. Oncotarget. 2014;5:12728–37. [DOI] [PubMed] [PMC]

170.

Shishodia G, Koul S, Dong Q, Koul HK. Tetrandrine (TET) Induces Death Receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5) and Sensitizes Prostate Cancer Cells to TRAIL-Induced Apoptosis. Mol Cancer Ther. 2018;17:1217–28. [DOI] [PubMed] [PMC]

171.

Sp N, Kang DY, Jo ES, Rugamba A, Kim WS, Park YM, et al. Tannic Acid Promotes TRAIL-Induced Extrinsic Apoptosis by Regulating Mitochondrial ROS in Human Embryonic Carcinoma Cells. Cells. 2020;9:282. [DOI] [PubMed] [PMC]

172.

Sang Eun H, Seong Min K, Ho Jeong L, Vetrivel P, Venkatarame Gowda Saralamma V, Jeong Doo H, et al. Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells. Nutrients. 2019;11:263. [DOI] [PubMed] [PMC]

173.

Chiu CF, Lin YQ, Park JM, Chen YC, Hung SW, Chiu CC, et al. The novel camptothecin derivative, CPT211, induces cell cycle arrest and apoptosis in models of human breast cancer. Biomed Pharmacother. 2020;128:110309. [DOI] [PubMed]

174.

Kim HJ, Seo BG, Kim KD, Yoo J, Lee JH, Min BS, et al. C5, A Cassaine Diterpenoid Amine, Induces Apoptosis via the Extrinsic Pathways in Human Lung Cancer Cells and Human Lymphoma Cells. Int J Mol Sci. 2020;21:1298. [DOI] [PubMed] [PMC]

175.

Wu J, Wood GS. Analysis of the Effect of Gentian Violet on Apoptosis and Proliferation in Cutaneous T-Cell Lymphoma in an In Vitro Study. JAMA Dermatol. 2018;154:1191–8. [DOI] [PubMed] [PMC]

176.

Chidambaram A, Sundararaju K, Chidambaram RK, Subbiah R, Jayaraj JM, Muthusamy K, et al. Design, synthesis, and characterization of α, β-unsaturated carboxylic acid, and its urea based derivatives that explores novel epigenetic modulators in human non-small cell lung cancer A549 cell line. J Cell Physiol. 2018;233:5293–309. [DOI] [PubMed]

177.

Wang Y, Guo S, Li D, Tang Y, Li L, Su L, et al. YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells. Cell Death Dis. 2020;11:242. [DOI] [PubMed] [PMC]

178.

Xiao R, Allen CT, Tran L, Patel P, Park SJ, Chen Z, et al. Antagonist of cIAP1/2 and XIAP enhances anti-tumor immunity when combined with radiation and PD-1 blockade in a syngeneic model of head and neck cancer. Oncoimmunology. 2018;7:e1471440. [DOI] [PubMed] [PMC]

179.

Deng Z, Gao P, Yu L, Ma B, You Y, Chan L, et al. Ruthenium complexes with phenylterpyridine derivatives target cell membrane and trigger death receptors-mediated apoptosis in cancer cells. Biomaterials. 2017;129:111–26. [DOI] [PubMed]

180.

Farghadani R, Seifaddinipour M, Rajarajeswaran J, Abdulla MA, Mohd Hashim NB, Khaing SL, et al. In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base β-diiminato manganese^III complex in hormone-dependent and triple negative breast cancer cells. PeerJ. 2019;7:e7686. [DOI] [PubMed] [PMC]

181.

Lee KC, Lee KF, Tung SY, Huang WS, Lee LY, Chen WP, et al. Induction Apoptosis of Erinacine A in Human Colorectal Cancer Cells Involving the Expression of TNFR, Fas, and Fas Ligand via the JNK/p300/p50 Signaling Pathway With Histone Acetylation. Front Pharmacol. 2019;10:1174. [DOI] [PubMed] [PMC]

182.

Dyari HRE, Rawling T, Chen Y, Sudarmana W, Bourget K, Dwyer JM, et al. A novel synthetic analogue of ω-3 17,18-epoxyeicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells. FASEB J. 2017;31:5246–57. [DOI] [PubMed]

183.

Nascimento FR, Baeta JVdPB, França AAPd, Oliveira MABRE, Pizziolo VR, Santos AAD, et al. Dibenzoylmethane derivative inhibits melanoma cancer in vitro and in vivo through induction of intrinsic and extrinsic apoptotic pathways. Chem Biol Interact. 2022;351:109734. [DOI] [PubMed]

184.

Kang TH, Yoon G, Kang IA, Oh HN, Chae JI, Shim JH. Natural Compound Licochalcone B Induced Extrinsic and Intrinsic Apoptosis in Human Skin Melanoma (A375) and Squamous Cell Carcinoma (A431) Cells. Phytother Res. 2017;31:1858–67. [DOI] [PubMed]

185.

Tung SY, Lee KC, Lee KF, Yang YL, Huang WS, Lee LY, et al. Apoptotic mechanisms of gastric cancer cells induced by isolated erinacine S through epigenetic histone H3 methylation of FasL and TRAIL. Food Funct. 2021;12:3455–68. [DOI] [PubMed]

186.

Chang KF, Huang XF, Chang JT, Huang YC, Weng JC, Tsai NM. Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor. Cancer Lett. 2020;495:180–90. [DOI] [PubMed]

187.

Yang DL, Zhang YJ, He LJ, Hu CS, Gao LX, Huang JH, et al. Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux. Biol Res. 2021;54:27. [DOI] [PubMed] [PMC]