Plumbagin-Induced Apoptosis of Human Breast Cancer Cells Is Mediated by Inactivation of NF-κB and Bcl-2
Plumbagin-Induced Apoptosis of Human Breast Cancer Cells Is Mediated by Inactivation of NF-κB and Bcl-2
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DOI：
10.1002/jcb.21966
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发表时间：
2008-12-15
影响因子：
4
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Ahmad, Aamir;Banerjee, Sanjeev;Sarkar, Fazlul H.
乳腺癌仍然是全世界女性癌症相关死亡的主要原因。乳腺癌的异质性使靶向治疗的进展进一步复杂化。三阴性乳腺癌缺乏雌激素受体、孕激素受体和 Her-2/neu (ErbB2)，是一种高度侵袭性乳腺癌亚型，难以治疗。多效性药物，例如自然界中发现的药物，可以靶向受体阳性和受体阴性的癌细胞，这表明此类药物可能对乳腺癌的预防和/或治疗产生重大影响。白花丹素（5-羟基-2-甲基-1, 4-萘醌）就是这样一种药物，对多种癌症具有抗肿瘤活性。然而，其抗乳腺癌的作用机制尚不清楚。我们假设白花丹素可能是对抗乳腺癌尤其是三阴性乳腺癌的有效药物。我们使用 ER 阳性 MCF-7 和 ER 阴性 MDA-MB-231（三阴性）乳腺癌细胞测试了我们的假设，我们发现白花丹素显着抑制乳腺癌细胞的生长，而对正常乳腺上皮细胞没有影响。我们还发现，白花丹素诱导细胞凋亡，同时使 Bcl-2 和 NF-kappa B 的 DNA 结合活性失活。Bcl-2 过度表达导致白花丹素诱导的作用减弱，表明白花丹素抑制细胞生长和诱导细胞凋亡部分是由于 NF-kappa B/Bcl-2 途径失活。据我们所知，这是第一份报告，显示了白花丹素在乳腺癌细胞中的机制和癌细胞特异性凋亡诱导作用，表明白花丹素在预防和/或治疗乳腺癌中的潜在作用。 J.细胞。生物化学。 105: 1461-1471, 2008。(C) 2008 Wiley-Liss, Inc.
Breast cancer remains the major cause of cancer-related deaths in women world-wide. The heterogeneity of breast cancer has further complicated the progress of target-based therapies. Triple negative breast cancers, lacking estrogen receptor, progesterone receptor and the Her-2/neu (ErbB2), represent a highly aggressive breast cancer subtype, that are difficult to treat. Pleiotropic agents, such as those found in nature, can target receptor-positive as well as receptor-negative cancer cells, suggesting that such agents could have significant impact in breast cancer prevention and/or therapy. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) is one such agent which has anti-tumor activity against several cancers. However, its mechanism of action against breast cancer is not clearly understood. We hypothesized that plumbagin may act as an effective agent against breast cancer especially triple negative breast cancer. We tested our hypothesis using ER-positive MCF-7 and ER-negative MDA-MB-231 (triple negative) breast cancer cells, and we found that plumbagin significantly inhibits the growth or breast cancer cells with no effect on normal breast epithelial cells. We also found that plumbagin induces apoptosis with concomitant inactivation of Bcl-2 and the DNA binding activity of NF-kappa B. Bcl-2 over-expression resulted in attenuation of plumbagin-induced effects, Suggesting that the inhibition of cell growth and induction of apoptosis by plumbagin is in part due to inactivation of NF-kappa B/Bcl-2 pathway. To our knowledge, this is the first report, showing mechanistic and cancer cell specific apoprosis-inducing effects of plumbagin in breast cancer cells, suggesting the potential role of plumbagin in the prevention and/or treatment of breast cancer. J. Cell. Biochem. 105: 1461-1471, 2008. (C) 2008 Wiley-Liss, Inc.