Antitumor Activity Of Curcumin Derivative FM04 And Its Mechanism

Objective: Curcumin, a yellow pigmentin turmeric (Curaumalonga), has been reported to have several pharmacological effects including anti-tumor, anti-inflammatory, and anti-oxidant properties[1]. Resently, its anti-carcinogenic properties seem to raise the most interest. One potential problem with the clinical use of curcumin is its low potency and poor absorption characteristics, and the systemic bioavailability of curcumin is low[2]. We have developed new synthetic derivatives of curcumin FM04, remained theβ-diketone, to enhance the biological activity. The present study focused on evaluating the antitumor effect of FM04 in vitro and the inhibitory effects on the animal transplanted tumor, and then the mechanism of apoptosis induced by FM04 in K562 cells was investigated Preliminary.Method: 1.Antitumor effect of FM04 in vitro MTT was used to determine the proliferative effects of FM04 on tumor cells; Colony assay was to observe the cell colony forming units(CFUs); AO/EB fluorescent staining was to detect the apoptotic rate; FITC-Annexin-V/PI flow cytometry was used to detect apoptosis. 2. Inhibition of tumor growth in vivo by FM04 Intraperitoneal injection of FM04(50mg/kg) was performed every day for ten days, and observe the inhibitory effects of FM04 on Mouse B16 Melanoma. 3. Mechanism of antitumor effect induced by FM04 The abundance of signal protein molecules expressed in K562 cells was examined by western blot. And the spectrophotometric detect kit was used to detect the activity of Caspase-3 and Caspase-9.Result: 1.Antitumor effect of FM04 in vitro FM04 inhibited many tumor cells growth with time- and dose-dependent manners; FM04 inhibited K562 CFUs and showed dose-dependent manner. 2. Inhibition of tumor growth in vivo by FM04 Intraperitoneal injection of FM04(50mg/kg) was performed every day for ten days, Mouse B16 Melanoma was sensitive to FM04, 50mg/kg FM04 treatment resulted in 54.1%(P<0.05) inhibition of tumor growth compared with untreated control. 3. Mechanism of antitumor effect induced by FM04 The abundance of P2l0bcr/abl as well as the downstream signal protein were strongly down-regulated in small dose of FM04-treated K562 cells; FM04 induced cytosolic accumulation of cytochrome c and activities of caspase-3/9, triggering apoptosis of K562 cell.Conclusion: FM04 exhibits stronger activity in antitumor in vitro and in vivo , and exhibits stronger activity of down-regulation of the abundance of P2l0bcr/abl and other proteins,and by inducing the release of cytochrome C from mitochondria and activing the caspase cascades.