Abstract. Curcumin (CUR) is a natural agent that has been demonstrated to effectively inhibit prostate cancer growth. However, natural CUR is relatively unstable and can be easily degraded in vivo. Therefore, it is essential to develop other stable curcuminoids. Demethoxycurcumin (DMC) is a candidate that has been verified in several tumor types and has potential for the treatment of prostate cancer. In the present study, we investigated the effects of DMC on proliferation, apoptosis and migration of PC-3 cells. MTT assay results indicated that DMC inhibited PC-3 cell viability in a dose-and time-dependent manner, and DMC induced G2/M phase arrest. Furthermore, PC-3 cells in DMC-treated groups had a higher apoptotic rate compared with DMSO-treated control. This effect may be due to the activation of the caspase-3 pathway. In DMC-treated groups, migrating and invasive cells were dramatically reduced (P<0.05). The activity of MMP-2, which is correlated with migration and invasion was also suppressed by DMC. These results indicated that DMC may inhibit PC-3 cell migration and invasion partially by affecting MMP-2 activity. In conclusion, DMC significantly inhibits proliferation, migration and invasion of cultured PC-3 cells, and this study may provide evidence for future in vivo studies and clinical use.
IntroductionProstate cancer is a common urologic malignant tumor, which is threatening more and more people currently. The emerging studies on cancer prevention and treatment with natural products expand the traditional treatment of prostate cancer (1). Curcuminoids are phenolic coloring compounds that can be extracted from the rhizomes of Curcuma longa linn. Curcumin (CUR), a member of curcuminoids, has potent anti-tumor effects to prostate cancer (2-4) and several other cancers, such as breast (5) and colon cancer (6). However, CUR can be easily degraded both in vitro and in vivo (7,8). The anti-tumor activity of CUR will be enormously reduced, and this instability property of CUR limits its clinical use in cancer treatment. It is feasible to develop new stable compounds that are structurally similar as CUR but without the loss of anti-tumor activity. Demethoxycurcumin (DMC), an analogue of CUR, is one of such compounds. In comparison with CUR, the structure of DMC lacks one methoxy group directly linking to the benzene ring (Fig. 1). Although the structure difference between CUR and DMC is slight, the chemical characteristics of DMC is more stable (9,10). Previous studies have reported that DMC could inhibit renal and breast cancer cell growth (11,12) and induce G2/M phase arrest and apoptosis in human glioma U87 cells (13). These studies provide evidence that DMC might be a good substitute for CUR in cancer treatment. However, the effects of DMC on prostate cancer cells still remain unclear. Therefore, the present study was designed to investigate the effects of DMC on proliferation, apoptosis, migration and invasion in cultured human prostate cancer cells. In order to further explore the mechanisms of DMC on c...