Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Isoxanthohumol exerts anticancer activity against drug-resistant thyroid cancer cells by inhibiting cell migration and invasion, apoptosis induction and targeting PI3K/AKT/m-TOR signaling pathway

Xiliang Zhang, Xiaodong Yang, Zhen Cao, Zhanwei Zhao, Yuxing Zhang

Department of General Surgery, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China;

For correspondence:- Yuxing Zhang Email: doctor_zyx1984@163.com Tel:+861066958114

Accepted: 22 May 2021 Published: 30 June 2021

Citation: Zhang X, Yang X, Cao Z, Zhao Z, Zhang Y. Isoxanthohumol exerts anticancer activity against drug-resistant thyroid cancer cells by inhibiting cell migration and invasion, apoptosis induction and targeting PI3K/AKT/m-TOR signaling pathway. Trop J Pharm Res 2021; 20(6):1151-1157 doi: 10.4314/tjpr.v20i6.8

© 2021 The authors.
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Abstract

Purpose: To investigate the anticancer effect of isoxanthohumol against drug-resistant thyroid cancer cells. Its effect on cellular PI3K/AKT/m-TOR signaling pathway, cell migration and invasion and apoptosis were also analyzed.

Methods: The cytotoxicity of isoxanthohumol drug was examined by MTT assay. Cellular morphology was assessed by phase contrast microscopy. Fluorescence microscopy and western blotting were used to evaluate its effect on cellular apoptosis. Further, western blotting was used to monitor the levels of expression of proteins linked to PI3K/AKT/m-TOR signaling pathway.

Results: Isoxanthohumol significantly (p<0.05) inhibited the proliferation and progression of drug-resistant human papillary BCPAP cancer cells in a concentration- and time-dependent manner. Further, morphological assessment of BCPAP cells indicate that there were proapoptotic alterations after isoxanthohumol treatment. The results for apoptosis in BCPAP cells showed enhanced number of apoptotic cells, elevated levels of proapoptotic proteins (including Bax), and increased level of expressions of caspase-3 and caspase-9. Isoxanthohumol targeted metastatic features of BCPAP cells by inhibiting both cell migration and cell invasion in a concentration-dependent manner. Western blotting revealed remarkable inhibition of PI3K/AKT/m-TOR signalling pathway through blocking of expression of its allied proteins.

Conclusion: Isoxanthohumol exhibits potent anticancer effect in human papillary cancer cells by inducing apoptosis, inhibition of cell migration, as well as invasion and targeting PI3K/AKT/m-TOR signalling pathway. These findings could play a significant role in drug design and discovery for thyroid cancer. However, more conformational investigations are required.

Keywords: Thyroid cancer, Drug resistance, Flavonoids, Isoxanthohumol, Apoptosis