Nicotine increases cancer stem cell population in MCF-7 cells.
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.
Division of Pharmacology, National Institute of Health Sciences, Setagaya 158-8501, Japan.
Naoya
N
Hirata
Yuko
Y
Sekino
Yasunari
Y
Kanda
D000444:Aldehyde Dehydrogenase / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D000072056:Transcription Factor HES-1; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000444:Aldehyde Dehydrogenase; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D018398:Homeodomain Proteins; D009538:Nicotine; D011978:Receptors, Nicotinic; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C078493:HES1 protein, human