Division of Pharmacology, National Institute of Health Sciences, Setagaya 158-8501, Japan.
Biochem Biophys Res Commun. 2010 Dec 3;403(1):138-43. doi: 10.1016/j.bbrc.2010.10.134. Epub 2010 Nov 3.
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 α7 subunit-selective antagonist of nicotinic acetylcholine receptors (nAChR) α-Bungarotoxin. These data suggest that nicotine increases the stem cell population via α7-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.
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未完全阐明。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,我们使用醛脱氢酶(ALDH)作为癌症干细胞标志物,通过流式细胞术研究了尼古丁对 MCF-7 人乳腺癌细胞中癌症干细胞群体的影响。结果发现,尼古丁呈剂量依赖性地增加 ALDH 阳性细胞群体。我们进一步证明,蛋白激酶 C-Notch 通路参与了尼古丁的作用。此外,尼古丁的作用可被烟碱型乙酰胆碱受体(nAChR)α7 亚单位选择性拮抗剂α-银环蛇毒素阻断。这些数据表明,尼古丁通过 MCF-7 细胞中的α7-nAChR 和蛋白激酶 C-Notch 依赖性途径增加干细胞群体。这些发现揭示了尼古丁与人类乳腺癌中癌症干细胞之间的关系。