Open AccessFlorofangchinoline inhibits proliferation of osteosarcoma cells via targeting of histone H3 lysine 27 trimethylation and AMPK activation
Author(s) -
Liyan Zhao,
Xiong-Tao Liu,
Wenwen Zhu,
Pei Ming Yang,
Jie Qin,
Ru Gu,
Zhili Zhao
Publication year - 2020
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v19i7.10
Subject(s) - apoptosis , annexin , flow cytometry , histone h3 , chemistry , viability assay , osteosarcoma , microbiology and biotechnology , cell growth , ampk , poly adp ribose polymerase , cancer research , histone , biology , kinase , biochemistry , polymerase , protein kinase a , dna
Purpose: To investigate the effect of florofangchinoline on osteosarcoma cell growth in vitro, and the underlying mechanism of action.Methods: Changes in the viability of KHOS and Saos-2 cells were measured using water soluble tetrazolium salt (WST) assay, while apoptosis was determined using Annexin V/PI staining and flow cytometry. Increases in mtDNA, and expressions of PGC-1α and TFAM were assayed with immunoblot analysis and quantitative real-time polymerase chain reaction (qPCR), respectively.Results: Microscopic examination of florofangchinoline-treated cells showed significant decrease in cell density, relative to control cells (p < 0.05). Treatment with 10 μM florofangchinoline increased apoptosis in KHOS and Saos-2 cells to 56.32 and 63.75 %, respectively (p < 0.05). Florofangchinoline treatment markedly enhanced cleavage of caspase-3, caspase-8, caspase-9 and PARP. It elevated Bax level and reduced Bcl-2 in KHOS and Saos-2 cells. Moreover, florofangchinoline increased p21 and p-AMPKα levels, and mtDNA counts in KHOS and Saos-2 cells (p < 0.05). Moreover, in florofangchinoline-treated KHOS cells, the expressions of EED, EZH2 and SUZ12 were significantly suppressed (p < 0.05).Conclusion: Florofangchinoline inhibits osteosarcoma cell viability by activation of apoptosis. Moreover, it activates AMPK and down-regulates histone H3 lysine 27 trimethylation in osteosarcoma cells. Therefore, florofangchinoline has potentials for development as a therapeutic drug forosteosarcoma.
Keywords: Osteosarcoma, Histone H3, Florofangchinoline, Apoptosis, Chemotherapeutic