A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-03, Vol.22 (3), p.472
• Main Authors: Weng, Jing-Ru, Bai, Li-Yuan, Lin, Wei-Yu, Chiu, Chang-Fang, Chen, Yu-Chang, Chao, Shi-Wei, Feng, Chia-Hsien
• Format: Article
• Language: English
• Subjects: Acetylation; Bacteria; Biocompatibility; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell cycle; Cell Cycle - drug effects; cell cycle arrest; Cell division; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Effectors; Female; flavone; Flavones - chemistry; Flavones - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Leukemia; M Phase Cell Cycle Checkpoints; MCF-7 Cells; Myoporaceae; Myoporum - chemistry; Myoporum bontioides; Oral cancer; Plant Extracts - chemistry; Plant Extracts - pharmacology; Signal transduction; Signal Transduction - drug effects
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22030472

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 (IC ) 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.