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.

Aims: In clinical practice, herbal medicines have played an important role in the modulation of drug transporters through the combination of conventional prescription drugs, which necessitates the elucidation of herb-drug interactions. The present study was designed to investigate the inhibitory effects and mechanisms of benzaldehyde, vanillin, muscone, and borneol on P-glycoprotein (P-gp). Methods: The effects of the 4 compounds on the intracellular accumulation of rhodamine-123 (Rho-123) in vinblastine-treated Caco-2 (VB-Caco-2) cells were studied by monitoring fluorescence intensity through a flow cytometry assay, and the effects of these compounds on Rho-123 transport through VB-Caco-2 monolayers and Rho-123 intestinal absorption in the rat everted gut sac were investigated by high-performance liquid chromatography. Moreover, P-gp expression in VB-Caco-2 cells was assessed using flow cytometry and Western blot analysis, and the relative ABCB1 mRNA level was determined by Real-time RT-PCR. Key Findings: The results showed that benzaldehyde, vanillin, muscone, and borneol significantly increased Rho-123 uptake in VB-Caco-2 cells, increased the absorption rate and apparent permeability coefficient of Rho-123 in rat jejunum and ileum, and decreased the efflux ratio of Rho-123 from 6.52 to less than 2 during transport across VB-Caco-2 cell monolayers. In addition, these compounds reduced the protein and ABCB1 mRNA levels of P-gp in VB-Caco-2 cells. Conclusions: These data indicate that benzaldehyde, vanillin, muscone and borneol could effectively reverse multidrug resistance via inhibiting the P-gp function and expression pathway. The data provide fodder for further investigation into the interaction between the 4 compounds and other drugs transported by P-gp.

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