Department of Biochemistry, Chiang Mai University, Thailand.
Arch Pharm Res. 2010 Jul;33(7):989-98. doi: 10.1007/s12272-010-0703-6. Epub 2010 Jul 27.
Matrix metalloproteinase-3 (MMP-3) is a key enzyme with important implications in the invasion and metastasis of breast cancer cells. Curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are major forms of curcuminoids found in turmeric powder with reported anticancer activity. This study focuses on the comparative effect of Cur, DMC and BDMC on the modulation of MMP-3 activity and its secretion in MDA-MB-231 breast cancer cells. MMP-3 levels were determined by casein zymography, ELISA and western blotting. Analysis of MMP-3 expression by casein zymography revealed high expression in MDA-MB-231 invasive breast carcinoma cells, but not in MCF-7 non-invasive breast cancer cells. ELISA assays showed MMP-3 levels were significantly decreased in all curcuminoid treatments. Using zymography, treatment with non-toxic doses revealed that every curcuminoid compound except Cur reduced MMP-3 levels. Moreover, the result from western blot analysis confirmed that only DMC and BDMC reduced MMP-3 secretion in MDA-MB-231 cells, but Cur did not have any effect. MMP-3 activity revealed that none of the curcuminoids showed significant effects. However, treatment of the cells with Cur, DMC and BDMC exhibited a significant inhibition of cell invasion and motility with DMC and BDMC being more potent. These results suggest that Cur, DMC, and BDMC may be used as MMP-3 inhibitors to modulate MMP-3 expression.
基质金属蛋白酶-3(MMP-3)是一种关键酶,对乳腺癌细胞的侵袭和转移具有重要意义。姜黄素(Cur)、脱甲氧基姜黄素(DMC)和双脱甲氧基姜黄素(BDMC)是姜黄粉中主要的姜黄素类化合物,具有报道的抗癌活性。本研究重点研究了姜黄素、DMC 和 BDMC 对 MDA-MB-231 乳腺癌细胞 MMP-3 活性及其分泌的调节作用。通过明胶酶谱法、ELISA 和 Western blot 测定 MMP-3 水平。明胶酶谱法分析 MMP-3 表达显示,MDA-MB-231 侵袭性乳腺癌细胞中 MMP-3 表达水平较高,而 MCF-7 非侵袭性乳腺癌细胞中则较低。ELISA 检测结果表明,所有姜黄素类化合物处理均可显著降低 MMP-3 水平。用无细胞毒性剂量的明胶酶谱法发现,除 Cur 外,所有姜黄素类化合物均可降低 MMP-3 水平。此外,Western blot 分析结果证实,只有 DMC 和 BDMC 可降低 MDA-MB-231 细胞中 MMP-3 的分泌,但 Cur 则没有影响。MMP-3 活性表明,没有一种姜黄素类化合物表现出显著的效果。然而,用 Cur、DMC 和 BDMC 处理细胞可显著抑制细胞侵袭和运动,而 DMC 和 BDMC 的作用更强。这些结果表明,Cur、DMC 和 BDMC 可作为 MMP-3 抑制剂,调节 MMP-3 的表达。