Cheah Yew Hoong, Azimahtol Hawariah Lope Pihie, Abdullah Noor Rain
Bioassay Unit, Herbal Medicine Research Center, Institute for Medical Research, 50588 Jalan Pahang, Kuala Lumpur, Malaysia.
Anticancer Res. 2006 Nov-Dec;26(6B):4527-34.
Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza Roxb (Zingiberaceae). Xanthorrhizol was tested for a variety of important pharmacological activities including antioxidant and anti-inflammatory activities. An antiproliferation assay using the MTT method indicated that xanthorrhizol inhibited the proliferation of the human breast cancer cell line, MCF-7, with an EC50 value of 1.71 microg/ml. Three parameters including annexin-V binding assay, Hoechst 33258 staining and accumulation of sub-G1 population in DNA histogram confirmed the apoptosis induction in response to xanthorrhizol treatment. Western-blotting revealed down-regulation of the anti-apoptotic bcl-2 protein expression. However, xanthorrhizol did not affect the expression of the pro-apoptotic protein, bax, at a concentration of 1 microg/ml, 2.5 microg/ml and 5 microg/ml. The level of p53 was greatly increased, whilst PARP-1 was cleaved to 85 kDa subunits, following the treatment with xanthorrhizol at a dose-dependent manner. These results, thereby, suggest that xanthorrhizol has antiproliferative effects on MCF-7 cells by inducing apoptosis through the modulation of bcl-2, p53 and PARP-1 protein levels.
姜黄醇是从姜科植物郁金（Curcuma xanthorrhiza Roxb）的根茎中分离得到的一种天然倍半萜类化合物。对姜黄醇进行了多种重要药理活性的测试，包括抗氧化和抗炎活性。采用MTT法进行的抗增殖试验表明，姜黄醇抑制人乳腺癌细胞系MCF-7的增殖，其半数有效浓度（EC50）值为1.71微克/毫升。膜联蛋白V结合试验、Hoechst 33258染色以及DNA直方图中亚G1期细胞群的积累这三个参数证实了姜黄醇处理可诱导细胞凋亡。蛋白质免疫印迹法显示抗凋亡蛋白bcl-2的表达下调。然而，在浓度为1微克/毫升、2.5微克/毫升和5微克/毫升时，姜黄醇并未影响促凋亡蛋白bax的表达。在用姜黄醇处理后，p53水平大幅升高，同时聚（ADP-核糖）聚合酶-1（PARP-1）被切割成85 kDa的亚基，且呈剂量依赖性。因此，这些结果表明姜黄醇通过调节bcl-2、p53和PARP-1蛋白水平诱导细胞凋亡，从而对MCF-7细胞具有抗增殖作用。
