Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Florofangchinoline inhibits proliferation of osteosarcoma cells via targeting of histone H3 lysine 27 trimethylation and AMPK activation

Liyan Zhao¹, Xiongtao Liu¹, Weina Zhu³, Pei Yang³, Jiexing Qin³, Ru Gu¹, Zhili Zhao⁴

¹Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital); ²Department of Anesthesia Surgery, PLA Air Force 986 Hospital; ³Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital); ⁴Department of Orthopedics, PLA Air Force 986 Hospital, Xi'an, Shaanxi 710004, China.

For correspondence:-

Accepted: 17 June 2020 Published: 31 July 2020

Citation: Zhao L, Liu X, Zhu W, Yang P, Qin J, Gu R, et al. Florofangchinoline inhibits proliferation of osteosarcoma cells via targeting of histone H3 lysine 27 trimethylation and AMPK activation. Trop J Pharm Res 2020; 19(7):1403-1409 doi: 10.4314/tjpr.v19i7.10

© 2020 The authors.
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Abstract

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 for osteosarcoma.

Keywords: Osteosarcoma, Histone H3, Florofangchinoline, Apoptosis, Chemotherapeutic