2,2'-diphenyl-3,3'-diindolylmethane: a potent compound induces apoptosis in breast cancer cells by inhibiting EGFR pathway.
2,2'-diphenyl-3,3'-diindolylmethane: a potent compound induces apoptosis in breast cancer cells by inhibiting EGFR pathway.
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DOI：
10.1371/journal.pone.0059798
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ghosh MK
中科院分区：
文献类型：
--
作者：
Bhowmik A;Das N;Pal U;Mandal M;Bhattacharya S;Sarkar M;Jaisankar P;Maiti NC;Ghosh MK
尽管医学最近取得了进展，但 30-40% 的乳腺癌患者出现复发，这凸显了改进有效治疗的必要性。在这项研究中，通过体外筛选，我们选择了一种新型合成吲哚衍生物2,2'-二苯基-3,3'-二吲哚基甲烷（DPDIM）作为潜在的抗乳腺癌药物。 DPDIM 在体外乳腺癌细胞 MCF7、MDA-MB 231 和 MDA-MB 468 中诱导细胞凋亡，在体内在 7,12-二甲基苯并[α]蒽 (DMBA) 诱导的 Sprague-Dawley (SD) 大鼠乳腺肿瘤中诱导细胞凋亡。我们的体外研究表明，DPDIM 通过负向调节 EGFR 及其下游分子（如 STAT3、AKT 和 ERK1/2）的活性来发挥细胞凋亡作用，这些分子参与这些癌细胞的增殖和存活。计算机预测还表明 DPDIM 可能在 EGFR 的 ATP 结合位点结合。 DPDIM 还抑制 EGF 诱导的细胞活力增加。我们还发现，在体外和体内 DPDIM 处理的细胞中，促生存因子 Bcl-XL 的表达降低，并且促凋亡蛋白（如 Bax、Bad、Bim）水平增加。我们的结果进一步表明，DPDIM 诱导的细胞凋亡是通过涉及 caspase 级联的线粒体凋亡途径介导的。据我们所知，这是 DPDIM 抗癌活性的第一份报告。总而言之，该报告表明 DPDIM 可能是乳腺癌的有效治疗剂。
Despite recent advances in medicine, 30–40% of patients with breast cancer show recurrence underscoring the need for improved effective therapy. In this study, by in vitro screening we have selected a novel synthetic indole derivative 2,2'-diphenyl-3,3'-diindolylmethane (DPDIM) as a potential anti- breast cancer agent. DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB 468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM exerts apoptotic effect by negatively regulating the activity of EGFR and its downstream molecules like STAT3, AKT and ERK1/2 which are involved in the proliferation and survival of these cancer cells. In silico predictions also suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore inhibits EGF induced increased cell viability. We have also shown decreased expression of pro-survival factor Bcl-XL as well as increase in the level of pro-apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in vivo. Our results further indicate that the DPDIM induced apoptosis is mediated through mitochondrial apoptotic pathway involving the caspase-cascade. To the best of our knowledge this is the first report of DPDIM for its anticancer activity. Altogether this report suggests that DPDIM could be an effective therapeutic agent for breast cancer.
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影响因子：
4.8
作者：
Guturi, Kiran Kumar Naidu;Mandal, Tapashi;Ghosh, Mrinal K.
通讯作者：
Ghosh, Mrinal K.
影响因子：
4.8
作者：
Ahmed, Syed Feroj;Deb, Satamita;Ghosh, Mrinal K.
通讯作者：
Ghosh, Mrinal K.
影响因子：
11.5
作者：
Diaz, N;Minton, S;Muro-Cacho, CA
通讯作者：
Muro-Cacho, CA
DOI：
10.1073/pnas.95.5.2648
发表时间：
1998-03-03
影响因子：
11.1
作者：
Chen, JH;Bander, JA;Iyengar, R
通讯作者：
Iyengar, R
影响因子：
8
作者：
Ghosh, MK;Sharma, P;Haque, SJ
通讯作者：
Haque, SJ