Exploration of Targeted Anti-tumor Therapy

Drug (name)	Cancer treated	Mechanism to increase ROS	References
Platinum drugs	Breast cancer (in combination with PARP inhibitors)	ROS-dependent DNA damage	[8, 9]
Imatinib	Melanoma	Loss of mitochondrial membrane potential	[10]
Doxorubicin	Kaposi’s sarcoma, breast, and bladder cancer	Fenton’s reaction and electron leakage	[11]
5-Fluorouracil	Colon and rectal cancer	P53 dependent ROS	[12, 13]

Declarations

Author contributions

RS: Conceptualization, Supervision. IGC: Supervision. PG: Conceptualization, Data curation, Formal analysis, Writing—original draft, 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

Rosner JL, Storz G. Regulation of bacterial responses to oxidative stress. Curr Top Cell Regul. 1997;35:163–77. [DOI] [PubMed]

Demple B. Study of redox-regulated transcription factors in prokaryotes. Methods. 1997;11:267–78. [DOI] [PubMed]

Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52:192–203. [DOI] [PubMed] [PMC]

Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863:2977–92. [DOI] [PubMed]

Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab. 2014;2:17. [DOI] [PubMed] [PMC]

Kim J, Kim J, Bae JS. ROS homeostasis and metabolism: a critical liaison for cancer therapy. Exp Mol Med. 2016;48:e269. [DOI] [PubMed] [PMC]

Sahu P, Camarillo IG, Sundararajan R. Enhanced antiproliferation potency of electrical pulse-mediated metformin and cisplatin combination therapy on MDA-MB-231 cells. Appl Biochem Biotechnol. 2022;194:18–36. [DOI] [PubMed]

Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AOH, Zander SAL, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008;105:17079–84. [DOI] [PubMed] [PMC]

Berndtsson M, Hägg M, Panaretakis T, Havelka AM, Shoshan MC, Linder S. Acute apoptosis by cisplatin requires induction of reactive oxygen species but is not associated with damage to nuclear DNA. Int J Cancer. 2007;120:175–80. [DOI] [PubMed]

10.

Chang SP, Shen SC, Lee WR, Yang LL, Chen YC. Imatinib mesylate induction of ROS-dependent apoptosis in melanoma B16F0 cells. J Dermatol Sci. 2011;62:183–91. [DOI] [PubMed]

11.

Kotamraju S, Chitambar CR, Kalivendi SV, Joseph J, Kalyanaraman B. Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endothelial cells: role of oxidant-induced iron signaling in apoptosis. J Biol Chem. 2002;277:17179–87. [DOI] [PubMed]

12.

Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3:330–8. [DOI] [PubMed]

13.

Hwang PM, Bunz F, Yu J, Rago C, Chan TA, Murphy MP, et al. Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells. Nat Med. 2001;7:1111–7. [DOI] [PubMed] [PMC]

14.

Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer—expanded options, evolving needs. Nat Rev Clin Oncol. 2022;19:91–113. [DOI] [PubMed]

15.

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34. [DOI] [PubMed]

16.

Sahu P, Giri P, Sunkara R, Sundararajan R. Extraction of key features and enhanced prediction framework of breast cancer occurrence. International Conference on Trends in Electronics and Informatics (ICEI). 2022 6th international conference on trends in electronics and informatics (ICOEI); 2022 Apr 28–30; Tirunelveli, India. Piscataway: IEEE; 2022. p. 1679–16. [DOI]

17.

Otto AM. Warburg effect(s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism. Cancer Metab. 2016;4:5. [DOI] [PubMed] [PMC]

18.

Younas M, Hano C, Giglioli-Guivarc’H N, Abbasi BH. Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives. RSC Adv. 2018;8:29714–44. [DOI] [PubMed] [PMC]

19.

Bhat KPL, Kosmeder JW 2nd, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001;3:1041–64. [DOI] [PubMed]

20.

Frémont L. Biological effects of resveratrol. Life Sci. 2000;66:663–73. [DOI] [PubMed]

21.

Carter LG, D’Orazio JA, Pearson KJ. Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer. 2014;21:R209–25. [DOI] [PubMed] [PMC]

22.

Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493–506. [DOI] [PubMed]

23.

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218–20. [DOI] [PubMed]

24.

Pirola L, Fröjdö S. Resveratrol: one molecule, many targets. IUBMB Life. 2008;60:323–32. [DOI] [PubMed]

25.

Chatterjee A, Ronghe A, Padhye SB, Spade DA, Bhat NK, Bhat HK. Antioxidant activities of novel resveratrol analogs in breast cancer. J Biochem Mol Toxicol. 2018;32:e21925. [DOI] [PubMed]

26.

Balasubramanian D, Girigoswami A, Girigoswami K. Nano resveratrol and its anticancer activity. Curr Appl Sci Technol. 2023;23:1–16. [DOI]

27.

Pozo-Guisado E, Lorenzo-Benayas MJ, Fernández-Salguero PM. Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor α-dependent mechanism: relevance in cell proliferation. Int J Cancer. 2004;109:167–73. [DOI] [PubMed]

28.

Pozo-Guisado E, Merino JM, Mulero-Navarro S, Lorenzo-Benayas MJ, Centeno F, Alvarez-Barrientos A, et al. Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-κB. Int J Cancer. 2005;115:74–84. [DOI] [PubMed]

29.

Haltiwanger S. Why electroporation is a useful technique for cancer treatments. In: Sundararajan R, editor. Electroporation-based therapies for cancer. Woodhead Publishing; 2014. pp. 103–25. [DOI]

30.

Dermol-Černe J, Pirc E, Miklavčič D. Mechanistic view of skin electroporation – models and dosimetry for successful applications: an expert review. Expert Opin Drug Deliv. 2020;17:689–704. [DOI] [PubMed]

31.

Batista Napotnik T, Polajžer T Miklavčič D. Cell death due to electroporation – a review. Bioelectrochemistry. 2021;141:107871. [DOI] [PubMed]

32.

Charoo NA, Rahman Z, Repka MA, Murthy SN. Electroporation: an avenue for transdermal drug delivery. Curr Drug Deliv. 2010;7:125–36. [DOI] [PubMed]

33.

Sersa G, Cemazar M, Rudolf Z. Electrochemotherapy: advantages and drawbacks in treatment of cancer patients. Cancer Ther. 2003;1:133–42.

34.

Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. Eur J Surg Oncol. 2008;34:232–40. [DOI] [PubMed]

35.

Wezgowiec J, Kotulska M, Saczko J, Derylo MB, Teissie J, Rols MP, et al. Cyanines in photodynamic reaction assisted by reversible electroporation—in vitro study on human breast carcinoma cells. Photodiagnosis Photodyn Ther. 2013;10:490–502. [DOI] [PubMed]

36.

Gehl J. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. Acta Physiol Scand. 2003;177:437–47. [DOI] [PubMed]

37.

Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, et al. Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European standard operating procedures of electrochemotherapy) study. EJC Suppl. 2006;4:3–13. [DOI]

38.

Campana LG, Miklavčič D, Bertino G, Marconato R, Valpione S, Imarisio I, et al. Electrochemotherapy of superficial tumors – current status: basic principles, operating procedures, shared indications, and emerging applications. Semin Oncol. 2019;46:173–91. [DOI] [PubMed]

39.

Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, et al. Potential adverse effects of resveratrol: a literature review. Int J Mol Sci. 2020;21:2084. [DOI] [PubMed] [PMC]

40.

Montgomery DC. Design and analysis of experiments. 10th ed. Wiley; 2020.

41.

Abdi H, Williams LJ. Honestly significant difference (HSD) test. In: Salkind N, editor. Encyclopedia of research design. New York: SAGE; 2010.

42.

Sebaugh JL. Guidelines for accurate EC50/IC50 estimation. Pharm Stat. 2011;10:128–34. [DOI] [PubMed]

43.

Giri P, Camarillo IG, Sundararajan R. Enhanced induction of MDA-MB-231 cell death using the combination of galloflavin and electroporation. Biointerface Res Appl Chem. 2023;13:263. [DOI]

44.

Giri P, Camarillo IG, Mitta L, Sundararajan R. Quantitative proteomic assessment of key proteins regulated by electrical pulse-mediated galloflavin delivery in triple-negative breast cancer cells. Biointerface Res Appl Chem. 2023;13:297. [DOI]

45.

Sundararajan R, Giri P, Madhivanan S, Ramesh A, Kishore NK, Manjunatha M, et al. Cisplatin-based electrochemotherapy significantly downregulates key heat shock proteins in MDA-MB-231-human triple-negative breast cancer cells. Appl Biochem Biotechnol. 2022;194:517–28. [DOI] [PubMed]

46.

Nunes XP, Silva FS, Guedes da Silva Almeida JR, Lima J, Ribeiro LAA, Quintans Júnior LJ, et al. Biological oxidations and antioxidant activity of natural products. In: Rao V, editor. Phytochemicals as nutraceuticals - global approaches to their role in nutrition and health. Intech; 2012. pp. 1–20. [DOI]

47.

Mandal P, Goswami A, Adhikari S, Sarkar S. Targeting oxidative stress in cancer. In: Chakraborti S, Ray BK, Roychoudhury S, editor. Handbook of oxidative stress in cancer: mechanistic aspects. Singapore: Springer; 2022. pp. 217–40. [DOI]

48.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603–16. [DOI] [PubMed] [PMC]

49.

Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer. 2003;3:276–85. [DOI] [PubMed]

50.

Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5:415–8. [DOI] [PubMed]

51.

Fukai T, Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020;9:1849. [DOI] [PubMed] [PMC]

52.

Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO. Mitogen-activated protein kinases and reactive oxygen species: how can ROS activate MAPK pathways? J Signal Transduct. 2011;2011:792639. [DOI] [PubMed] [PMC]

53.

Giri P, Mittal L, Camarillo IG, Sundararajan R. Analysis of pathways in triple-negative breast cancer cells treated with the combination of electrochemotherapy and cisplatin. Biointerface Res Appl Chem. 2021;11:13453–64. [DOI]

54.

Penninger JM, Kroemer G. Mitochondria, AIF and caspases — rivaling for cell death execution. Nat Cell Biol. 2003;5:97–9. [DOI] [PubMed]

55.

Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U, et al. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood. 2007;109:2293–302. [DOI] [PubMed]

56.

Das J, Ramani R, Suraju MO. Polyphenol compounds and PKC signaling. Biochim Biophys Acta. 2016;1860:2107–21. [DOI] [PubMed] [PMC]

57.

Tong SY, Lee JM, Ki KD, Choi YJ, Seol HJ, Lee SK, et al. Correlation between FDG uptake by PET/CT and the expressions of glucose transporter type 1 and hexokinase II in cervical cancer. Int J Gynecol Cancer. 2012;22:654–8. [DOI] [PubMed]

58.

Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez JC, Moreno-Sánchez R. Kinetics of transport and phosphorylation of glucose in cancer cells. J Cell Physiol. 2009;221:552–9. [DOI] [PubMed]

59.

Jung KH, Lee JH, Thien Quach CH, Paik JY, Oh H, Park JW, et al. Resveratrol suppresses cancer cell glucose uptake by targeting reactive oxygen species-mediated hypoxia-inducible factor-1a ativation. J Nucl Med. 2013;54:2161–7. [DOI] [PubMed]

60.

Subramanian L, Youssef S, Bhattacharya S, Kenealey J, Polans AS, van Ginkel PR. Resveratrol: challenges in translation to the clinic — a critical discussion. Clin Cancer Res. 2010;16:5942–8. [DOI] [PubMed] [PMC]

61.

Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004;24:2783–840. [PubMed]

62.

Sareen D, Darjatmoko SR, Albert DM, Polans AS. Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer. Mol Pharmacol. 2007;72:1466–75. [DOI] [PubMed]

63.

Mondal A, Bennett LL. Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage. Biomed Pharmacother. 2016;84:1906–14. [DOI] [PubMed]

64.

Cheng T, Wang C, Lu Q, Cao Y, Yu W, Li W, et al. Metformin inhibits the tumor-promoting effect of low-dose resveratrol, and enhances the anti-tumor activity of high-dose resveratrol by increasing its reducibility in triple negative breast cancer. Free Radic Biol Med. 2022;180:108–20. [DOI] [PubMed]