Curcumin Enhances Cytotoxicity of Chemotherapeutic Agents in Prostate Cancer Cells by Inducing P21(Waf1/Cip1) and C/Ebpbeta Expressions and Suppressing Nf-Kappab Activation
Resource
PROSTATE v.51 n.3 pp.211-218
Journal
PROSTATE
Journal Volume
v.51
Journal Issue
n.3
Pages
211-218
Date Issued
2002
Date
2002
Author(s)
CHEN, JUN
HUANG, CHAO-YUAN
PU, YEONG- SHIAU
Abstract
BACKGROUND: The modulatory effects and molecular mechanisms of curcumin ( CCM) on the cytotoxicity of chemotherapeutic agents to prostate cancer cells were explored. METHODS: The combined effects of CCM and chemotherapeutic agents were examined by three different administration schedules (one concurrent and two sequential treatments) in two androgen- independent prostate cancer (AIPC) cells (PC-3 and DU145). Alteration of cell cycle progression, protein levels, and transcriptional activation in PC-3 cells were assayed by flow cytometry, Western blotting, and gel shift assay, respectively. RESULTS: The combined effects of CCM --> chemotherapeutic agent schedule showed the greatest synergistic cytotoxicity when compared to the other two schedules in both cells. CCM induced a significant G1 arrest in PC-3, which may be mediated by the induction of p21(WAF1 /CIP1) and C/EBPbeta. Moreover, CCM was able to inhibit both the constitutional and TNF-alpha-induced NF-kappaB activation in a time-dependent manner. CONCLUSIONS: The incorporation of CCM into cytotoxic therapies may be a promising strategy for the treatment of AIPC. Copyright 2002 Wiley-Liss, Inc.
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