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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.

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. MicroRNAs have been shown to be correlated with biological processes of various tumors. In this study, we observed that the expression of miR-582-5p was lower in NSCLC tissues than that in para-carcinoma tissues. Ectopic expression of miR-582-5p significantly inhibited NCI-H358 cell proliferation and invasion. Knockdown of miR-582-5p showed the opposite results, with cell growth rate and the invasive capacity of PC-9 cells enhanced. Furthermore, we elucidated that NOTCH1 is a target of miR-582-5p and there is an inverse correlation between miR-582-5p and NOTCH1 expression in NSCLC tissues. Overexpression of NOTCH1 in miR-582-5p-overexpressing NCI-H358 cells could partially reverse the inhibition of cell proliferation and invasion by miR-582-5p. Thus, our research demonstrated that miR-582-5p suppresses NSCLC cell lines’ growth and invasion via targeting oncoprotein NOTCH1 and restoration of miR-582-5p might be feasible therapeutic strategy for NSCLC.

Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M.Gillett (G. acuta) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against myocardial damage. However, the effects and mechanisms of BEL on myocardial fibrosis have not been reported. In vivo, BEL dampened isoprenaline (ISO)-induced cardiac structure disturbance and collagen deposition. In vitro, BEL inhibited transforming growth factor (TGF)-β1-induced cardiac fibroblast (CF) proliferation. In vivo and in vitro, BEL decreased the expression of α-smooth muscle actin (α-SMA), collagen Ⅰ and Ⅲ, and inhibited TGF-β1/Smads signaling. Additionally, BEL impeded p38 activation and NR4A1 (an endogenous inhibitor for pro-fibrogenic activities of TGF-β1) phosphorylation and inactivation in vitro. In CFs, inhibition of p38 by SB203580 inhibited the phosphorylation of NR4A1 and did not limit Smad3 phosphorylation, and blocking TGF-β signaling by LY2157299 and SB203580 could decrease the expression of α-SMA, collagen I and III. Overall, both cell and animal studies provide a potential role for BEL against myocardial fibrosis by inhibiting the proliferation and phenotypic transformation of CFs. These inhibitory effects might be related to regulating TGF-β1/Smads pathway and p38 signaling and preventing NR4A1 cytoplasmic localization.

Gentianella acuta (G. acuta) is one of the most commonly used herbs in Chinese Mongolian medicine for the treatment of heart disease. Previously, it was found that G. acuta ameliorated cardiac function and inhibited isoproterenol (ISO)-induced myocardial fibrosis in rats. In this study, the underlying anti-fibrotic mechanism of G. acuta was further elucidated. Histopathological changes in the heart were observed by hematoxylineosin, Masson trichrome and wheat germ agglutinin staining. Relevant molecular events were investigated using immunohistochemistry and western blotting. The results revealed that G. acuta caused improvements in myocardial injury and fibrosis. G. acuta also inhibited collagens I and III and α-smooth muscle actin production in heart tissue. G. acuta downregulated the expression of transforming growth factor β1 (TGF-β1) and notably inhibited the levels of phosphorylation of TGF-β receptors I and II. Furthermore, G. acuta caused downregulation of the intracellular mothers against decapentaplegic homolog (Smads)2 and 4 expression and inhibited Smads2 and 3 phosphorylation. The results further demonstrated that the mechanism underlying anti-myocardial fibrosis effects of G. acuta was based upon the suppression of the TGF-β1/Smads signaling pathway. Therefore, G. acuta may be a potential therapeutic agent for ameliorating myocardial fibrosis.