Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways.
Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways.
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DOI：
10.1038/srep23077
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发表时间：
2016-03-15
影响因子：
4.6
通讯作者：
Ahmed K
中科院分区：
文献类型：
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作者：
Afsar T;Trembley JH;Salomon CE;Razak S;Khan MR;Ahmed K
海岛相思因其在多种疾病中的药用而闻名。在这项研究中，我们进行了生物测定指导的细胞毒性化合物的分离，并研究了它们对前列腺癌和乳腺癌细胞系生长和信号活性的影响。鉴定了4种活性多酚化合物：7-O-没食子酸儿茶素(GC)、儿茶素(C)、没食子酸甲酯(MG)和儿茶素-3-O-没食子酸酯(CG)。四种化合物以剂量依赖方式抑制前列腺癌PC-3细胞的生长，而CG和MG则抑制乳腺癌MDA-MB-231细胞的生长。所有被测试的化合物都抑制了两种细胞系的细胞存活和集落生长，并且有证据表明染色质凝集、细胞收缩和凋亡小体。丫啶橙、溴化乙锭、碘化丙啶和DAPI染色显示PC-3和MDA-MB-231细胞的部分死亡是通过细胞凋亡发生的。在PC-3细胞中，药物处理抑制了抗凋亡分子Bcl2、Bclxl和Survivin的表达，同时下调了AKT、NFJAKB、ERK1/2和κ/STAT信号通路。在MDAMB-2 31细胞中，药物诱导CK2α、Bclxl、Survivin和XIAP蛋白表达降低，并抑制了NFJAK/STAT和PI3K信号通路。我们的发现表明，从海藻中提取的某些多酚类化合物可能是有希望的抗癌化学预防/治疗候选化合物。
Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer.