title: A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells.
abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4'-dimethoxy-3',5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50) values ranging from 3.3 μM (MCF-7) to 8.6 μM (SCC4). Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1's modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2), CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2) and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.
authors.affiliation: Department of Marine Technology and Resources, National Sun-Yat-sen University, Kaohisung 804, Taiwan. columnster@gmail.com.
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Weng
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan. lybai6@gmail.com.|College of Medicine, China Medical University, Taichung 404, Taiwan. lybai6@gmail.com.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.affiliation: Department of Pharmacy, Kinmen Hospital, Kinmen 891, Taiwan. d5686@mail.cmuh.org.tw.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: College of Medicine, China Medical University, Taichung 404, Taiwan. u8557006@yahoo.com.tw.|Cancer Center, China Medical University Hospital, Taichung 404, Taiwan. u8557006@yahoo.com.tw.
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. wind-chen@yahoo.com.tw.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. south102411@gmail.com.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Chao
authors.affiliation: Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chfeng@cc.kmu.edu.tw.
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Feng
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D061986:MCF-7 Cells; D031643:Myoporum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047309:Flavones; D010936:Plant Extracts
keywords: Myoporaceae; Myoporum bontioides; breast cancer; cell cycle arrest; flavone