Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo.
We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P < 0.05 by two-way ANOVA). For example, 26 days after tumor cell implantation, the average tumor volume in control mice (1025 +/- 205 mm3) was approximately 1.7-fold higher compared with AITC-treated mice. Histological analysis of tumors excised at the termination of the experiment revealed a statistically significant increase in number of apoptotic bodies with a concomitant decrease in cells undergoing mitosis in the tumors of AITC-treated mice compared with that of control mice. Western blot analysis indicated an approximately 70% reduction in the levels of anti-apoptotic protein Bcl-2 in the tumor lysate of AITC-treated mice compared with that of control mice. Moreover, the tumors from AITC-treated mice, but not control mice, exhibited cleavage of BID, which is known to promote apoptosis. Statistically significant reduction in the expression of several proteins that regulate G2/M progression, including cyclin B1, cell division cycle (Cdc)25B and Cdc25C (44, 45 and 90% reduction, respectively, compared with control), was also observed in the tumors of AITC-treated mice relative to control tumors. In conclusion, the results of the present study indicate that AITC administration inhibits growth of PC-3 xenografts in vivo by inducing apoptosis and reducing mitotic activity.
Srivastava
Sanjay K
SK
Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Xiao
Dong
D
Lew
Karen L
KL
Hershberger
Pamela
P
Kokkinakis
Demetrius M
DM
Johnson
Candace S
CS
Trump
Donald L
DL
Singh
Shivendra V
SV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D009368:Neoplasm Transplantation; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014675:Vegetables / Q000737:chemistry*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D017879:Isothiocyanates; C004471:allyl isothiocyanate