title: Antiproliferative and apoptosis-inducing activity of nobiletin against three subtypes of human breast cancer cell lines.
abstract: Although nobiletin has a potent antitumor activity against several types of human cancers, its inhibitory effects and possible mechanisms of action on breast cancer cells with different hormone receptor and HER2 status remains unknown.
  
  
  METHODS
  Using hormone receptor-positive MCF-7, HER2-positive SK-BR-3, and triple-negative MDA-MB-468 cell lines, we investigated the antitumor mechanisms of nobiletin.
  
  
  RESULTS
  Nobiletin exhibited dose- and time-dependent antitumor activity against these different subtypes of cell lines, with the greatest inhibition observed against the MDA-MB-468 cell line. Nobiletin induced cell-cycle arrest at the G0/G1 phase by suppressing ERK1/2 activity, with concomitant cyclin-D1 suppression and p21 up-regulation. Nobiletin induced apoptotic cell death by reducing Bcl-xL expression, without affecting Bax levels, and inhibited the activity of AKT and downstream mTOR in MDA-MB-468 cells, but not in other cell lines.
  
  
  CONCLUSIONS
  The predominant anticancer activity of nobiletin in MDA-MB-468 cells suggests a potential role of nobiletin for the prevention of triple-negative breast cancer.
authors.affiliation: Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, 5-7-1 Befu, Johnan-ku, Fukuoka, Fukuoka 814-0198, Japan. snakano@nakamura-u.ac.jp.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Misaki
authors.initials: M
authors.lastname: Ono
authors.forename: Mikako
authors.initials: M
authors.lastname: Takeshima
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakano
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D047309:Flavones; C008661:nobiletin
keywords: Apoptosis; G0/G1 arrest; breast cancer; nobiletin; triple-negative