Mechanism of action of PL against different cancers

CancerIn vitro/In vivoModelOutcome/MechanismReferences
ABC-DLBCLIn vitroOCI-Ly10, U2932, DB ↑p21, ↓NF-κB↑Apoptosis, ↓Bcl-2, ↓survivin, ↑Bax[122]
Bladder cancerIn vitro
In vivo		T24, BIU-87, EJ
T24 xenograft		G2/M phase arrest, ↓GSH
G2/M phase arrest, ↓β-catenin, ↓ ZEB1, ↓N-cadherin, ↓claudin-1, ↓ZO-1, ↓Slug		[123]
Biliary cancerIn vitroHuCCT-1, OCUG-1G2/M phase arrest, ↑apoptosis, ↑p-ERK, ↑LC3-II, ROS[112]
Breast cancerIn vitroMCF-7↓Akt/mTORC1, ↓GSK-3β, ↓TSC2, ↓4E-BP1, ↓p70S6K, ↑LC3-II, ↑autophagy[90]
In vitroMDA-MB-231, BT-549, Hs578TGrowth, ↓metastasis, ↓EMT, ↓ZEB1, ↓slug, ↑E-cadherin, ↓MMP2, ↓MMP9, ↑miR-200c, ↓IL-6, ↑ROS, ↑autophagy[120]
In vitroMDA-MB-468, MCF-7↓Proliferation, ↑G2/M arrest, ↑apoptosis, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8[116]
In vitroBT474, MCF7, SkBr3↓p-HER1, ↓p-HER2, ↓p-HER3, ↑ROS[126]
In vitroMCF-7, MCF-10A↑Apoptosis, ↑HO-1, ↑Nrf2[213]
In vitroMCF-7↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt[92]
In vivoMCF-7 xenograft↓tumor growth, ↓p-FOXO3A, ↑BIM[92]
In vitroSKBR3↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET[125]
In vitroMCF-7↓SETDB1, ↑FosB, ↑cleaved PARP, ↑caspase-9[117]
In vitroMCF-7↑E-cadherin, ↓snail1, ↓Twist1, ↓cyclin D1[121]
In vitroMCF-7↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα, ↓mRNA expression of cyclin B1, ↑mRNA p21 expression, ↓NF-κB activation[100]
Cervical cancerIn vitroHeLa↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt[92]
CCAIn vitroKKU-055, KKU-100, KKU-139, KKU-213, KKU-214G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,[113]
CRCIn vitroLOVO, SW480, HCT116, HT29, HCT8, SW620↓Cell viability, ↓clonogenic potential, ↓cyclin D1, ↓c-Fos, ↓p-EGFRTyr1068, ↓Akt, ↓ERK1/2[93]
In vivoHT-29-xenograft↓Tumor growth, ↓c-Fos and cyclin D1 positive cells[93]
In vitroSW-620↓Proliferation[116]
In vitroHCT 116, HCT 116 Bax−/−, HCT 116 p21−/−, HCT 116 p53−/−G2/M phase arrest, ↑apoptosis[131]
In vivoDMH & DSS induced↓Tumor growth, G2/M phase arrest, ↑apoptosis, ↓Bcl-2, ↑cleaved caspase-3, ↓Ras, ↓cyclin D1, ↓NF-κB[130]
In vitroDLD-1G2/M cell cycle arrest, ↑apoptosis, ↑ROS, ↓GSH, ↓TrxR[129]
In vitroHT29, SW620, HCT116↑Nrf2, ↑ROS, ↑Bax, ↑cleaved caspase-3, ↑cleaved PARP, ↑MDM2[132]
In vivoHT-29-xenograft↓Tumor growth, ↓tumor volume, ↓mutant p53, ↑Bax, ↑cleaved PARP[132]
In vitroHT-29, HCT 116↑Apoptosis, ↑p-ERK[114]
In vivoAOM/DSS induced↓COX-2, ↓IL-6, ↓β-catenin, ↓snail[128]
In vitroHCT116↑apoptosis, ↑p-c-Jun, JNK activation[133]
In vitroINT-407, HCT-116↑ROS, ↓FN1, ↓CDH2, ↓CTNNB1, ↓Bcl2, ↓survivin, ↑p53, ↑Bax, ↑SMAD4, ↑p21, ↓Twist[127]
Gastric cancerIn vitroAGS, HGC-27G2/M phase arrest, ↑GADD45α, ↑ROS[119]
In vitroSGC-7901, BGC-823↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis[135]
In vivoSGC-7901 xenograft↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA[135]
In vitroMKN45, AGSG2/M phase arrest, ↓p-JAK1, ↓p-JAK2, ↓p-STAT3, ↓Ki-67, ↓MMP-9, ↓Twist, ↓cyclin D1[109]
In vitroMGC-803↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt[92]
GliomaIn vitroHGG↑ROS, ↓PRDX4, ↑cleaved caspase-3, ↑P-H2AX, ↑CHOP, ↑p-eIF2α, ↑apoptosis[136]
In vitroU87MG↓Proliferation, ↑apoptosis, ↑FOS, ↑RAF1, ↑NFKB1, ↑NFKB1A, ↑NFKB2, ↑PIK3CA, ↑TP53, ↓AKT1, ↓AKT2, ↓DVL1, ↓EGFR, ↓PIK3R1, ↑PTEN, ↑BRAF, ↓KRAS[134]
HNCIn vitroUMSCC1, UMSCC10A, UMSCC17A↑Apoptosis, ↑LC3-II, ↑ROS, ↑8-oxo-dG, ↓GSTP1 activity[142]
In vivoUMSCC10A xenograft↓Tumor volume[142]
In vitroSAS, CGHNC8↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug[144]
In vivoSAS & CGHNC8 xenograft↓Tumor weight, ↓tumor growth[144]
In vitroOC2, OCSL↓Proliferation, ↑G0/G1 arrest, ↑p21, ↑apoptosis, ↑PARP-1, ↑caspase-3, ↑senescence[145]
HCCIn vitroHUH-7, HepG2↑ROS, ↓proliferation, ↑apoptosis, ↓procaspase-3, ↑Bax, ↑cleaved caspase-3, ↑G2/M arrest, ↑ATF4, ↑p-eIF2α, ↑p-PERK, ↓TrxR1, ↓Bcl-2[64]
In vivoHUH-7 xenograft↓Tumor volume and weight, ↑ROS, ↓TrxR1[64]
Lung cancerIn vitroA549↓Proliferation, ↑cell death, ↓migration[143]
In vitroA549, H1299↑Apoptosis, ↑ROS[138]
In vitroH1975, H23, HCC827↓HK2, ↑cleaved-PARP, ↑caspase-3[94]
In vivoH1975 & HCC827 xenograft↓p-Akt, ↓p-S6, HK2, ↓Ki-67, ↓tumor weight, ↓tumor growth[94]
In vitroA549, A549/DTX↑Cleaved PARP, ↓Bcl-2, ↑Bax, ↑LC3-II, ↑apoptosis, ↓p-Akt (Thr308 and Ser473), ↓PI3K, ↓mTOR (Ser2448)[95]
In vivoA549/DTX xenograft↓Tumor volume, ↓Ki-67, ↓p-Akt, ↓mTOR[95]
In vitroA549↑ROS, ↑LC3B-II[137]
In vitroA549↑Apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET[125]
In vitroA549, NCI-H460↑Apoptosis, ↑Bax, ↑cleaved caspase-3 and -8, ↓Bcl-2[102]
In vivoA549 xenograft↓Tumor volume, ↓tumor weight, ↑Fas, ↑DR4, ↑Bax, ↓Bcl-2, ↑cleaved caspase-3 and -8, ↓nuclear p50 and p65[102]
In vitroA549↑E-cadherin, ↓snail1, ↓Twist1[121]
In vitroA549G1 phase arrest, ↑ROS, ↓cyclin D1, ↓CDK6, ↑p-ERK1/2, ↓p-Akt, ↓p-Rb, ↓NF-κB p65 nuclear translocation, ↓Rb, ↓CDK4[91]
MMIn vitroOPM2, MM1R, U266, IM-9, NCI-H929↑Apoptosis, ↑caspase-3, -9, or -8 activity, ↑cyclin E, ↓Bcl-2, ↑Bax/Bcl-2, ↑ROS, ↓STAT3 activity, ↑p21, ↑p27, ↓c-myc, ↓cyclin A, ↓survivin[110]
Prostate cancerIn vitroPC-3, DU-145, LNCaP↓Proliferation, ↓NF-κB, ↓IL-6, ↓IL-8, ↓MMP-9, ↓invasion, ↓adhesion, ↓ICAM-1[101]
In vitroDU-145↓p-STAT3Tyr-705, ↓cyclin A, ↓survivin, ↑cleaved PARP, ↓cell survival, ↑G1/S arrest, ↑ERK1/2, ↓Bcl-2[111]
In vitroPC-3↓Akt/mTORC1, ↓GSK-3β, ↓TSC2, ↓p70S6K, ↑LC3-II, ↑autophagy, ↓4E-BP1[90]
Pancreatic cancerIn vitroMIAPaCa-2, PANC-1↑Cell death, ↑ROS[140]
In vitroPanc1, L3.6pL↑Apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4 ↓cMyc, ↓EGFR, ↓survivin, ↓cMET[125]
In vitroPANC-1, MIA PaCa-2↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1[85]
In vivoPANC-1 xenograft↓Tumor growth, ↓Ki67, ↑8-OHdG[85]
In vitroPANC-1, AsPC-1, BxPC-3↓c-Myc, ↓cyclin D1, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓VEGF, ↓MMP-9, ↓NF-κB, ↓survivin,[115]
In vivoBxPC-3 xenograft↓Tumor growth, ↓c-Myc, ↓cyclin D1, ↓Bcl-2, ↓survivin, ↓XIAP, ↓VEGF, ↓MMP-9, ↓NF-κB, ↓Bcl-xL[115]
In vitroMIA PaCa-2, PANC-1↓GST activity, ↑JNK activation, ↑c-Jun, ↑HMOX1, ↑HSPA1A, ↑Myc, ↑CASP3, ↑PIK3CG, ↓Bcl-2, ↓NF-κB1, ↓AKT3, ↑cleaved caspase-3, ↑cleaved PARP, ↑apoptosis, ↑ATF-2, ↑CDKN1A, ↓p-ERK[139]
RCCIn vitro786-O↓Akt/mTORC1, ↓GSK-3β, ↓TSC2, ↓p70S6K, ↑LC3-II, ↓4E-BP1[90]
In vitro786-O↑Apoptosis, ↑ ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET[125]
In vitro786-O, PNX0010↓cMET, ↓p-ERK1/2, ↓p-STAT3, ↓p-Akt, ↑ROS[146]
In vivoPTX xenograft↓Tumor growth, ↓cMET[146]
Skin cancerIn vitroA375, A875, B16-F10G2/M phase arrest, ↑apoptosis, ↑cleaved caspase-3, ↓Bcl-2, ↑Bax, ↑p-JNK, ↑ROS, ↑p21, ↑p27[141]

8-OHdG: 8-hydroxy-2’-deoxyguanosine; ABC-DLBCL: activated B cell-like subtype of diffuse large B cell lymphoma; ATF4: activating transcription factor-4; CCA: cholangiocarcinoma; Cdc: cell division control; CHOP: C/EBP homologous protein; CK18: cytokeratin 18; cMET: hepatocyte growth factor receptor; COX-2: cyclooxygenase-2; DMH: 1,2-dimethylhydrazine; DR4: death receptor 4; DSS: dextran sulfate sodium; DTX: docetaxel-resistant; EGFR: epidermal growth factor receptor; FOXO3A: forkhead box O3A; GST: GSH S-transferase; GSTP1: GST pi 1; HCC: hepatocellular carcinoma; HO-1: heme oxygenase-1; MDA: malondialdehyde; MM: multiple myeloma, MMP-9: matrix metalloproteinases-9; Nrf2: nuclear factor-erythroid-2-related factor-2; HK2: hexokinase 2; NQO1: NAD(P)H quinone dehydrogenase 1; p-eIF2α: phosphorylation of eukaryotic initiation factor-2α; PRDX4: peroxiredoxin 4; PTX: paclitaxel; Rb: retinoblastoma; RCC: renal cell carcinoma; SETDB1: SET domain bifurcated histone lysine methyltransferase 1; SOD: superoxide dismutase; SOX2: sex determining region Y-box 2; Sp: specificity protein; TrxR: thioredoxin reductase; VEGF: vascular endothelial growth factor; ZEB1: zinc finger E-box binding homeobox 1; ZO-1: zonula occludens-1