Lin Chin-Chung, Kuo Chao-Lin, Huang Yi-Ping, Chen Cheng-Yen, Hsu Ming-Jie, Chu Yung Lin, Chueh Fu-Shin, Chung Jing-Gung
Departments of Chinese Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Executive Yuan, Taichung, Taiwan, R.O.C.
General Education Center, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
Anticancer Res. 2018 May;38(5):2761-2769. doi: 10.21873/anticanres.12519.
BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the curcuminoids present in turmeric, has been shown to induce cell death in many human cancer cell lines, however, there has not been any investigation on whether DMC inhibits metastatic activity in human cervical cancer cells in vitro. In the present study, DMC at 2.5-15 μM decreased cell number, thus, we used IC (7.5 μM) for further investigation of its anti-metastatic activity in human cervical cancer HeLa cells.
The wound healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of DMC on HeLa cells.
The wound healing assay was used to show that DMC suppressed cell movement of HeLa cells. Furthermore, the trans-well chamber assay was used to show that DMC suppressed HeLa cell migration and invasion. Gelatin zymography assay did not show any significant effects of DMC on the gelatinolytic activity (MMP-2 and -9) in conditioned media of HeLa cells treated by DMC. Western blotting showed that DMC significantly reduced protein levels of GRB2, MMP-2, ERK1/2, N-cadherin and Ras but increased the levels of E-cadherin and NF-κB in HeLa cells. Confocal laser microscopy indicated that DMC increased NF-κB in HeLa cells confirming the results from Western blotting.
DMC may be used as a novel anti-metastatic agent for the treatment of human cervical cancer in the future.
背景/目的：去甲氧基姜黄素（DMC）是姜黄中含有的姜黄素类化合物之一，已被证明可诱导多种人类癌细胞系发生细胞死亡，然而，尚未有关于DMC在体外是否抑制人宫颈癌细胞转移活性的研究。在本研究中，2.5 - 15 μM的DMC可减少细胞数量，因此，我们使用7.5 μM的半数抑制浓度（IC）进一步研究其对人宫颈癌HeLa细胞的抗转移活性。
采用伤口愈合、迁移、侵袭、酶谱分析和蛋白质印迹分析等方法研究DMC对HeLa细胞的影响。
伤口愈合分析表明DMC抑制HeLa细胞的移动。此外，Transwell小室分析表明DMC抑制HeLa细胞的迁移和侵袭。明胶酶谱分析未显示DMC对经DMC处理的HeLa细胞条件培养基中的明胶分解活性（基质金属蛋白酶-2和-9）有任何显著影响。蛋白质印迹分析表明DMC显著降低HeLa细胞中GRB2、基质金属蛋白酶-2、细胞外信号调节激酶1/2、N-钙黏蛋白和Ras的蛋白水平，但增加E-钙黏蛋白和核因子κB的水平。共聚焦激光显微镜检查表明DMC增加HeLa细胞中的核因子κB，证实了蛋白质印迹分析的结果。
未来DMC可能用作治疗人类宫颈癌的新型抗转移药物。
