title: Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines.
abstract: Breast cancer is the second leading cause of cancer‑related mortality in females worldwide. Therefore, identifying alternative strategies to combat the disease mortality is important. The aim of the present study was to investigate the effect of tanshinone I (Tan I) on the tumorigenicity of estrogen‑responsive MCF‑7 and estrogen‑independent MDA‑MB‑453 human breast cancer cells. The cytotoxicity of Tan I was evaluated using a Cell Counting Kit‑8 assay, the apoptosis and cell cycle distribution were detected using flow cytometry and the cell morphology was observed using a fluorescence microscope. In addition, the cell cycle regulatory proteins and apoptosis‑associated proteins involved in the phosphatidylinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were detected using western blot analysis using specific protein antibodies. The MCF‑7 and MDA‑MB‑453 cells were equally sensitive to Tan I regardless of their responsiveness to estrogen. Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin‑dependent kinase inhibitors p21Cip1 and p27Kip1. In addition, Tan I was found to downregulate anti‑apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway. Notably, treatment with the PI3K inhibitor, LY294002, decreased the levels of phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR. These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D002867:Chromones; D018844:Cyclin-Dependent Kinases; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C021751:tanshinone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human