Flavokawain A inhibits prostate cancer cells by inducing cell cycle arrest and cell apoptosis and regulating the glutamine metabolism pathway.

Abstract

Flavokawain A (FKA), a major chalcone in kava extracts, has exhibited anti-proliferative and apoptotic effects in the prostate cancer. However, the molecular mechanism of FKA remains unclear. In this study, FKA induces cell apoptosis and cell cycle arrest in a G2M phase to prostate cancer cells. FKA interferes with tubulin polymerization and inhibits survivin expression in PC3 cells. Molecular docking simulation experiment finds that FKA can bind to colchicine binding sites that inhibit tubulin polymerization. FKA treatment regulates the glutamine metabolism pathway in PC3 cells by reducing intracellular glutamine, glutamic and proline. FKA treatment also decreases the GSH content by decreasing the activity of GSH synthetase (GSS) and increasing the activity of glutathione thiol transferase (GSTP1), which subsequently induces ROS production and PC3 cell apoptosis.

• Authors: Kaili Wang, Weijie Zhang, Zihan Wang, Ming Gao, Xinying Wang, Wenchao Han, Nan Zhang, Xia Xu
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 186 Pg. 113288 (Jul 15 2020) ISSN: 1873-264X [Electronic] England
• PMID: 32361091 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Tubulin
• flavokawain A
• Glutamine
• Chalcone
• GSTP1 protein, human
• Glutathione S-Transferase pi
• Glutathione Synthase
• Glutathione

Topics

• Apoptosis (drug effects)
• Binding Sites
• Chalcone (analogs & derivatives, pharmacology, therapeutic use)
• Drug Screening Assays, Antitumor
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Glutamine (metabolism)
• Glutathione (metabolism)
• Glutathione S-Transferase pi (metabolism)
• Glutathione Synthase (metabolism)
• Humans
• Male
• Metabolic Networks and Pathways (drug effects, genetics)
• Metabolomics
• Molecular Docking Simulation
• PC-3 Cells
• Prostate (pathology)
• Prostatic Neoplasms (drug therapy, genetics, pathology)
• Reactive Oxygen Species (metabolism)
• Tubulin (metabolism)