Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis.
Dietary isothiocyanates (ITCs) are highly effective in affording protection against chemically induced cancers in laboratory animals. In the present study, we demonstrate that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits proliferation of cultured PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC(50) of approximately 15-17 micro M. On the other hand, survival of a normal prostate epithelial cell line (PrEC) was minimally affected by AITC even at concentrations that were highly cytotoxic to the prostate cancer cells. Reduced proliferation of PC-3 as well as LNCaP cells in the presence of AITC correlated with accumulation of cells in G(2)/M phase and induction of apoptosis. In contrast, AITC treatment failed to induce apoptosis or cause G(2)/M phase arrest in PrEC cells. A 24 h treatment of PC-3 and LNCaP cells with 20 micro M AITC caused a significant decrease in the levels of proteins that regulate G(2)/M progression, including Cdk1 (32-50% reduction), Cdc25B (44-48% reduction) and Cdc25C (>90% reduction). A significant reduction in the expression of cyclin B1 protein (approximately 45%) was observed only in LNCaP cells. A 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing concentration of AITC (20 micro M) resulted in a significant decrease (31-68%) in the levels of anti-apoptotic protein Bcl-2 in both cell lines, and approximately 58% reduction in Bcl-X(L) protein expression in LNCaP cells. In conclusion, it seems reasonable to hypothesize that AITC, and possibly other ITCs, may find use in the treatment of human prostate cancers.
Xiao
Dong
D
Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
Srivastava
Sanjay K
SK
Lew
Karen L
KL
Zeng
Yan
Y
Hershberger
Pamela
P
Johnson
Candace S
CS
Trump
Donald L
DL
Singh
Shivendra V
SV
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014675:Vegetables / Q000737:chemistry*; D051020:bcl-X Protein; D020687:cdc25 Phosphatases / Q000378:metabolism
C494811:BCL2L1 protein, human; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C004471:allyl isothiocyanate; D016203:CDC2 Protein Kinase; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases