Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells

Abstract

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...

Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

“…Meanwhile, an increase in the sub-G 1 peak, which is an characteristic feature of cell apoptosis, was also induced by DMC, suggesting that G 2 /M arrest is an underlying mechanism inhibiting the growth of DMC-treated OSCC cells, which might further turn on an apoptotic program. These results are supported by other published studies which indicate that DMC markedly induced G 2 /M arrest in brain and prostate cancers [24,35]. Evidence in the literature indicates that DMC induced BCL-2-mediated G 2 /M arrest most effectively among CUR, DMC, and BDMC in brain tumors [24].…”

Demethoxycurcumin Preserves Renovascular Function by Downregulating COX‐2 Expression in Hypertension

“…Furthermore, previous studies using cancer cells and N9 microglial cells validated the safety of DMC at 10  μ mol/L [19, 20]. In vivo treatment with DMC had the effect to reduced IL-1 β in the ischemic brain.…”

Effects of demethoxycurcumin on the viability and apoptosis of skin cancer cells

“…DMC, which is a structural analogue of CUR, also exhibits antitumor effects (14) and strongly inhibits proliferation of prostate cancer cells (23). The improved stability of DMC compared to CUR may significantly prolong the time of action of DMC and extend its half-life, suggesting that DMC may be an attractive compound to explore as an anticancer agent.…”

“…Previous studies have demonstrated that DMC strongly inhibits proliferation in numerous types of cancer, including prostate cancer, kidney cancer and breast cancer cells (15–17). However, the effects of DMC on skin cancer cells remain unknown.…”