Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway

Abstract

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.

Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines

“…The antitumor action of coffee polyphenols has been investigated in tumor cell lines, pre-clinical, and clinical studies (Rajagopal et al, 2018). Chlorogenic acid induces apoptosis and selectively inhibits proliferation of A498 human renal cancer cells but not of HEK293 human embryonic kidney cells (Wang et al, 2019). Caffeic acid inhibits proliferation of hepatocellular carcinoma cells and SK-Mel-28 human melanoma cancer cells by inducing apoptosis (Brautigan et al, 2018), alters gene expression in SK-Mel-28 cells (Pelinson et al, 2019), and attenuates the properties of cancer stem cell-like cells by increasing DNA methylating and inducing the expression of miR-148a (Li et al, 2015).…”

Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid

“…Figure 2 and Figure 3 show possible modulations by CGA, although individual pathways in which CGA is involved have not necessarily been reported. Figure 2 illustrates CGA’s downregulation of ROS [ 2 , 11 , 48 , 120 , 127 ], DNA damage [ 123 ], EGFR [ 127 ], Akt/phosphatidyl 3-inositol kinase (PI3K) [ 127 ], ERK1/2 [ 11 , 127 ], NF-κB [ 2 , 121 , 125 , 127 , 128 ], TNF-α [ 2 , 122 ], IL-1β [ 122 ], IL-8 [ 2 , 11 ], IL-6 [ 122 ], MMPs [ 2 , 11 ], COX-2 [ 125 , 128 ], Bcl-2 [ 10 , 129 ], mTOR [ 10 , 127 ], VEGF [ 126 ], and upregulation of AMPK [ 7 , 49 ]. Although CGA’s upregulation of CaMKK and LKB1 shown in Figure 3 has not been determined yet, Park et al [ 130 ] reported upregulation of them by neochlorogenic acid, an isomer of CGA.…”

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

“…bladder, prostate, renal carcinoma, and breast cancer (Deka et al, 2017;Yamagata et al, 2018;Wang et al, 2019b) Gallic acid anti-proliferation AKT1, CCNA/B1/D1/D3/E, CDC25C/ 2C, CDK2/4/6, CDKN1A/1B, CHEK1/2, INK4, MAPK1/14, P18, PIK3CA, SKP2…”