Study On The Inhibitory Effect Of Curcumin And Berberine On Deoxycholic Acid Induced Cell Proliferation

Background & Aims: Many components derived from medicinal plants have been found to possess substantial chemopreventive properties. Curcumin and berberine have been shown to inhibit experimental carcinogenesis and mutagenesis, but the underlying molecular mechanisms of their chemopreventive activities remain unclear. Bile acid especially deoxycholic acid (DCA) has been considered to be the carcinogen of cancer. In the present work we assessed the effect of curcumin and berberine on DCA induced cell proliferation in human HT-29 colon cancer cell line to discuss their underlying anti-cancer mechanisms.Methods: Cultured HT-29 Colon cancer cells were divided into three groups (DCA, DCA and curcumin, DCA and berberine). The effect of curcumin and berberine on cell proliferation was studied using the method of MTT. RT-PCR was applied to measure cyclooxygenase-2 (COX-2) mRNA transcription. Cellular immunochemical stain (CIS) was applied, using a mouse anti-human COX-2 monoclonal antibody to label COX-2 protein expression. Radio immunoassay (RIA) was applied to assess prostaglandin E2 (PGE2) level in the culture medium.Results: 200 μ M DCA induced cell proliferation and COX-2 mRNA transcription.The inhibitory rate of 1 μ M curcumin in DCA induced cell proliferation was 8.75%. Curcumin at concentration higher than 0.5 μ M inhibited DCA induced COX-2 mRNA transcription at 12 hours. Curcumin at concentration higher than 1 μ M inhibited DCA induced COX-2 expression and PGE2 synthesis at 12-48 hours. 20 μ M curcumin led to maximal induction of COX-2 protein expression-4-and COX-2 mRNA transcription at 48 and 12 hours, respectively.The inhibitory rate of 1 u M berberine in DCA induced cell proliferation was 7.38%. Berberine at concentration higher than 1 u M inhibited DCA induced COX-2 mRNA transcription at 6 hours. Berberine at concentration higher than 1 u M inhibited DCA induced COX-2 expression and PGE2 synthesis at 12-48 hours. 20 u M berberine led to maximal induction of COX-2 protein expression and COX-2 mRNA transcription at 48 and 12 hours, respectively.There was no significant difference between Curcumin and berberine in inhibiting DCA induced cell proliferation and COX-2 expression. But berberine slightly made effort better than curcumin in inhibiting DCA induced COX-2 mRNA transcription.Conclusions: Treatment with curcumin and berberine suppressed DCA-mediated induction of cell proliferation. Curcumin and berberine also suppressed the induction of COX-2 mRNA transcription and COX-2 protein expression by DCA. These data provide new insights into the anti-cancer properties of curcumin and berberine.