Prostate cancer (PC) patients once Paclitaxel (TAX) treatment responsive later develop hormone refractory PC, thus becoming TAX-insensitive.
This underscores the urgent need to develop novel anti-PC therapies. Vernonia amygdalina (VA) could be one such candidate agent. We have shown that androgen-independent PC-3 cells are sensitive to VA treatment in vitro. VA extract (0.01, 0.1 and 1mg/ml) inhibited DNA synthesis by 12%, 45% (p<0.05), and 73% (p<0.01) respectively. In contrast, TAX (0.01, 0.1, and 1μM) failed to significantly affect cell growth, suggesting TAX resistance. We tested molecular mechanisms which may lend to the observed PC-3 cell VA sensitivity/TAX resistance. Though both VA and TAX stimulated MAPK activity, VA's induction was more intense, but transient, compared to TAX's sustained action. NF-κB activation was inhibited on average by 50% by either 1mg/ml VA or 1μM TAX. VA extract caused 35% and 45% increases in c-Myc activity at 10 and 60min intervals respectively, with the highest stimulation attained 1h after treatment. In contrast, similar levels were attained by TAX rapidly (within 5min) and were sustained compared to the slow/multi-phasic action of VA. VA extract treatments had no effect on AKT gene expression, while TAX treatments yielded a four-fold (P<0.01) increase; and P-glycoprotein (P-gp) activity was inhibited by VA and stimulated by TAX, compared to control (basal ATPase activity). This study shows that TAX-resistant PC-3 cells are sensitive to VA, perhaps explained by differential regulatory patterns of MAPK, c-Myc, AKT, and Pgp activities/expressions.
Written by:
Cameron KS, Howard CB, Izevbigie EB, Hill BJ, Tchounwou PB Are you the author?
The Laboratory of Cellular Signaling, Phytoceuticals, and Cancer Prevention and Therapies, United States; JSU/NIH-Center for Environmental Health, College of Science Engineering and Technology, United States
Reference: Exp Toxicol Pathol. 2012 Dec 10. pii: S0940-2993(12)00108-X(Epub ahead of print)
doi: 10.1016/j.etp.2012.11.002
PubMed Abstract
PMID: 23238229
