Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation.
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.
Hour
Tzyh-Chyuan
TC
Department of Urology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan, Republic of China.
Chen
Jun
J
Huang
Chao-Yuan
CY
Guan
Jing-Yi
JY
Lu
Shiu-Hui
SH
Pu
Yeong-Shiau
YS
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011268:Pregnancy-Specific beta 1-Glycoproteins; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016328:NF-kappa B; D011268:Pregnancy-Specific beta 1-Glycoproteins; D016329:Sp1 Transcription Factor; D004247:DNA; D003474:Curcumin