Nicotine increases cancer stem cell population in MCF-7 cells
Nicotine increases cancer stem cell population in MCF-7 cells
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DOI：
10.1016/j.bbrc.2010.10.134
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发表时间：
2010-12-03
影响因子：
3.1
通讯作者：
Kanda, Yasunari
中科院分区：
文献类型：
--
作者：
Hirata, Naoya;Sekino, Yuko;Kanda, Yasunari
流行病学研究表明吸烟与乳腺癌风险增加有关。尼古丁很可能与吸烟的风险有关。然而，尼古丁促进癌症发展的机制尚不完全清楚。最近有人提出，乳腺癌的发生起源于癌症干细胞，而癌症干细胞是乳腺癌的一小部分。在本研究中，我们使用流式细胞术和癌症干细胞标记物乙醛脱氢酶 (ALDH)，研究了尼古丁对 MCF-7 人乳腺癌细胞中癌症干细胞群体的影响。我们发现尼古丁以剂量依赖性方式增加 ALDH 阳性细胞数量。我们进一步证明 PKC-Notch 通路参与尼古丁的作用。此外，烟碱乙酰胆碱受体 (nAChR) α-金环蛇毒素的 α7 亚基选择性拮抗剂治疗可阻断尼古丁的作用。这些数据表明尼古丁通过 α7-nAChR 和 MCF-7 细胞中的 PKC-Notch 依赖性途径增加干细胞群。这些发现揭示了尼古丁与人类乳腺癌中的癌症干细胞之间的关系。 (C) 2010 Elsevier Inc. 保留所有权利。
Epidemiological studies have suggested that cigarette smoking is related to increased breast cancer risk. Nicotine is most likely related to the risk in cigarette smoking. However, the mechanisms by which nicotine promotes cancer development are not fully understood. It has recently been suggested that development of breast cancer are originated from cancer stem cells, which are a minor population of breast cancer. In the present study, we investigated the effects of nicotine on the population of cancer stem cells in MCF-7 human breast cancer cells, using flow cytometry with a cancer stem cell marker aldehyde dehydrogenase (ALDH). We found that nicotine increased ALDH-positive cell population in a dose-dependent manner. We further demonstrated that a PKC-Notch pathway is involved in the effect of nicotine. In addition, the effect of nicotine was blocked by treatment with the alpha 7 subunit-selective antagonist of nicotinic acetylcholine receptors (nAChR) alpha-Bungarotoxin. These data suggest that nicotine increases the stem cell population via alpha 7-nAChR and the PKC-Notch dependent pathway in MCF-7 cells. These findings reveal a relationship between nicotine and the cancer stem cells in human breast cancer. (C) 2010 Elsevier Inc. All rights reserved.