Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway.
J Pharm Pharmacol. 2019 Apr 15. Epub 2019 Apr 15. PMID: 30989669
OBJECTIVES: Kidney cancer is a highly lethal cancer, of which the most common type is renal cell carcinoma (RCC). The targeted drugs used in treating RCC clinically have a lot of side effects. Therefore, it is urgent to find out effective agents with little toxic effects.
METHODS: The antiproliferation effect of chlorogenic acid (CA) was performed using the CCK-8 assay. Then, we adopted colony formation assay, Annexin V/PI staining assay and JC-1 mitochondrial membrane potential assay to explore the mechanism of anticancer effect of CA. We also conducted qPCR and Western blot to determine the pathway involved.
KEY FINDINGS: We identified that CA selectively suppressed proliferation of human RCC cell line A498 but not the human embryonic kidney cell HEK293. Mechanistic studies showed that CA significantly induced apoptosis, as indicated by activation of caspase protein and increased ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 (P < 0.05). Furthermore, we found that PI3K/Akt/mTOR signalling pathway is involved in the inhibitory effect of CA on A498 cells. Activation of this pathway increased proliferation and decreased apoptosis of A498 cells, exhibiting antagonism function against CA.
CONCLUSION: Our research firstly reports the efficacy of CA against RCC cells and elucidates the underlying molecular mechanisms. These findings indicate that CA is a potential agent for treating RCC.