Review Article

A Perspective on Withania somnifera Modulating Antitumor Immunity in Targeting Prostate Cancer

Table 1

Nonimmune molecular targets of WFA and Withania somnifera (WS) root extract in prostate cancer.

Compound typeModel systemMolecular targets

Withaferin ALNCaP, PC3, and 22RV1 cell linesInduces cytoprotective autophagy by increasing GABARAPL1 (ATG8L) expression [11]
Withaferin APC3 cell lineInduction of prostate apoptosis response-4- (Par-4-) dependent apoptosis [14]
Withaferin APC3 and DU145 cell linesUpregulation of Aurora B, phosphor histone H3, and phospho-Wee-1 expression and downregulation of cyclins (A2, B1, and E2) and phospho-Chk1 (Ser345), Chk2 (Thr68), and Cdc2 (Tyr15) [22]
Withaferin ACell lines PC3, DU145, and LNCaPDisrupt vimentin cytoskeleton by induction of ROS and c-Fos expression and suppression of c-FLIP(L) [23]
Withaferin ALNCaP cells and PC3 xenografts in nude mice, i.p. injection with 4 or 8 mg/kg/day for 24 daysTarget β5 subunit and inhibition of chymotrypsin-like activity in vivo tumors of PC3 xenografts with an accumulation of proteasome target proteins (p27, Bax, and IκB-α) and decreased AR protein in in vitro LNCaP cell line [32]
Withaferin ATRAMP model, oral gavage of 5 mg/kgPrevent prostate adenocarcinoma, inhibit AKT signaling, and activate Foxo3a-Par-4-induced cell death and EMT markers (vimentin, β-catenin, and snail and upregulate E-cadherin) [44]
Withaferin APten-KO mice, oral gavage with 3 or 5 mg/kgInhibit primary tumor growth and lung metastasis, downregulation of pAKT-mediated EMT markers [46]
Withaferin A and ethanol extract of WS rootLNCaP and 22RV1 cell linesInhibits fatty acid synthesis by decreasing fatty acid metabolism enzymes: acetyl-CoA carboxylase 1, ATP citrate lyase, carnitine palmitoyltransferase 1A, and fatty acid synthase with a decrease in c-Myc and pAKT [49]
WS root extractPC3 cell lineInhibit expression levels of cyclooxygenase-2 and interleukin-8 [50]

AR: androgen receptor; EMT: epithelial-to-mesenchymal transition; i.p.: intraperitoneal; LPS: lipopolysaccharides; PARP: poly (ADP-ribose) polymerase; ROS: reactive oxygen species; TRAMP: transgenic adenocarcinoma of mouse prostate.