Department of Pathology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Center, Detroit, MI 48201, USA.
J Cell Biochem. 2010 Apr 15;109(6):1134-41. doi: 10.1002/jcb.22492.
Garcinol, obtained from Garcinia indica in tropical regions, is used for its numerous biological effects. Its anti-cancer activity has been suggested but the mechanism of action has not been studied in-detail, especially there is no report on its action against breast cancer cells. Here we tested our hypothesis that garcinol may act as an anti-proliferative and apoptosis-inducing agent against breast cancer cell lines. Using multiple techniques such as MTT, Histone-DNA ELISA, Annexin V-PI staining, Western blot for activated caspases and cleaved PARP, homogenous caspase-3/7 fluorometric assay and EMSA, we investigated the mechanism of apoptosis-inducing effect of garcinol in ER-positive MCF-7 and ER-negative MDA-MB-231 cells. We found that garcinol exhibits dose-dependent cancer cell-specific growth inhibition in both the cell lines with a concomitant induction of apoptosis, and has no effect on non-tumorigenic MCF-10A cells. Our results suggested induction of caspase-mediated apoptosis in highly metastatic MDA-MB-231 cells by garcinol. Down-regulation of NF-kappaB signaling pathway was observed to be the mechanism of apoptosis-induction. Garcinol inhibited constitutive NF-kappaB activity, which was consistent with down-regulation of NF-kappaB-regulated genes. This is the first report on anti-proliferative and apoptosis-inducing action of garcinol against human breast cancer cells and the results suggest that this natural compound merits investigation as a potential chemo-preventive/-therapeutic agent, especially against breast cancer.
姜黄素是从热带地区的藤黄果实中提取的，具有多种生物活性。其抗癌活性已被提出，但作用机制尚未详细研究，特别是其对乳腺癌细胞的作用尚无报道。在这里，我们检验了这样一个假设，即姜黄素可能作为一种抗增殖和诱导细胞凋亡的试剂，作用于乳腺癌细胞系。我们使用 MTT、组蛋白-DNA ELISA、Annexin V-PI 染色、活化 caspase 和 cleaved PARP 的 Western blot、caspase-3/7 荧光比色分析和 EMSA 等多种技术，研究了姜黄素在 ER 阳性 MCF-7 和 ER 阴性 MDA-MB-231 细胞中诱导细胞凋亡的作用机制。结果发现，姜黄素对这两种细胞系均表现出剂量依赖性的肿瘤细胞特异性生长抑制作用，同时诱导细胞凋亡，对非致瘤性 MCF-10A 细胞没有影响。我们的结果表明，姜黄素诱导高转移性 MDA-MB-231 细胞发生 caspase 介导的凋亡。我们观察到 NF-κB 信号通路的下调是诱导凋亡的机制。姜黄素抑制了 NF-κB 的组成性活性，这与 NF-κB 调节基因的下调一致。这是首次报道姜黄素对人乳腺癌细胞具有抗增殖和诱导凋亡的作用，研究结果表明，这种天然化合物值得作为一种潜在的化学预防/治疗药物进行研究，特别是针对乳腺癌。
