PFG acted as an inducer of premature senescence in TIG-1 normal diploid fibroblast and an inhibitor of mitosis in the HeLa cells

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2019-06, Vol.83 (6), p.986-995
• Main Authors: Huang, Ying, Ohno, Osamu, Miyamoto, Kenji
• Format: Article
• Language: English
• Subjects: anti-proliferative; beta-Galactosidase - metabolism; cell cycle arrest; Cell Cycle Checkpoints - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Cellular Senescence - drug effects; Diploidy; DNA Damage - drug effects; Dose-Response Relationship, Drug; Enzyme Activation; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - enzymology; Flow Cytometry; Fluorescent Antibody Technique; Free Radical Scavengers - pharmacology; HeLa Cells; Humans; Mitosis - drug effects; Monoterpenes - administration & dosage; Monoterpenes - isolation & purification; Monoterpenes - pharmacology; Paeonia - chemistry; Paeoniflorigenone; reactive oxygen species; Reactive Oxygen Species - metabolism; senescence
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2019.1585744

Our previous work has reported an anti-proliferative compound from moutan cortex, paeoniflorigenone which can induce cancer-selective apoptosis. However, its anti-proliferative mechanism is still unknown. According to morphology changes (hypertrophy and flattening), we hypothesized that PFG can induce senescence or inhibit cell mitosis. Here we show that PFG can induce cellular senescence, evidenced by the expression of senescence-associated β-galactosidase, G0/G1 cell cycle arrest and permanent loss of proliferative ability, in normal TIG-1 diploid fibroblast but not cancerous HeLa cells. In cancerous HeLa cells, PFG inhibited proliferation by inducing S and G2/M cell cycle arrest and mitosis inhibition. DNA damage response was activated by PFG, interestingly the reactive oxygen species level was suppressed instead of escalated. To sum up, we report 3 new roles of PFG as, 1. inducer of premature senescence in normal TIG-1 cells, 2. inhibitor of mitosis in cancerous HeLa cells, 3. ROS scavenger. Abbreviations: PFG: Paeoniflorigenone; ROS: reactive oxygen species; ATM: ataxia telangiectasia mutated; t-BHP: tert-butyl hydroperoxide; SA-β-gal: senescence-associatedβ-galactosidase; DNA-PK cs : DNA-dependent protein kinase; γ-H2AX: H2AX phosphoryla-tion at Ser-139 Paeoniflorigenone induced senescence in normal cells, inhibited mitosis and induced apoptosis in cancerous cells to show anti-proliferative effect.