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Objectives: To investigate the function and regulatory mechanisms of delphinidin in the treatment of hepatocellular carcinoma. Methods: HepG2 and HuH-7 cells were treated with different concentrations of delphinidin. Cell viability was analysed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell autophagy and autophagic flux were analysed by LC3b-green fluorescent protein (GFP)-Adv and LC3b-GFP-monomeric red fluorescent protein-Adv transfected HepG2 and HuH-7 cells, respectively. Cell apoptosis was analysed by Hoechst33342 staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and DNA laddering. Cell autophagy, apoptosis and survival related protein expressions were detected by Western blotting. Key findings: After treatment with different concentrations of delphinidin, the cell survival rate was significantly decreased. Delphinidin could block the autophagic flux, resulting in a significant increase in autophagosomes, and led to an increase in cell apoptosis. The combined application of delphinidin and cisplatin could promote the antitumour effect and reduce the dose of cisplatin in tumour cells. Further mechanism studies reveal that delphinidin could inhibit the multidrug resistance gene 1 (MDR1) and the tumour-promoting transcription cofactor DEAD-box helicase 17 (DDX17) expression in tumour cells. Overexpression of DDX17 could reverse delphinidin's antitumor function in tumour cells. Conclusions: Delphinidin has a strong anti-tumour effect by inducing tumour cell autophagic flux blockage and apoptosis by inhibiting of both MDR1 and DDX17 expression. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline that has excellent anticancer effects during tumor chemotherapy, but it can cause cardiotoxic effects and its clinical use has been limited. Therefore, finding new drugs or methods to prevent or reverse the cardiac damage caused by DOX therapy in cancer patients is essential. Previous studies have identified potential cardioprotective effects of Centella asiatica ( C. asiatica ), and madecassic acid (MA) is a pentacyclic triterpenoid derived from C. asiatica . However, the pharmacological effects of MA on the heart and tumors during tumor chemotherapy are not fully understood. The aim of this study was to investigate the pharmacological function and molecular mechanisms of MA in the heart and tumor during chemotherapy. In a DOX-induced acute heart failure mouse model and a cardiomyocyte injury model, MA reduced cardiomyocyte oxidative stress and the inflammatory response, improved mitochondrial function, and attenuated autophagic flux blockade and apoptosis. Interestingly, MA significantly increased the expression and activity of SIRT1. When SIRT1 was knocked down, the protective effect of MA on cardiomyocytes was significantly inhibited, suggesting that MA may exert cardioprotective effects through the SIRT1 pathway. Interestingly, in contrast to its cardioprotective effect, MA could synergize with DOX and significantly contribute to the anticancer chemotherapeutic effect of DOX by inhibiting proliferation, migration and invasion; promoting apoptosis; and suppressing tumor progression by inhibiting the expression of the DDX5 pathway in tumor cells. Here, we identified the pharmacological functions of the pentacyclic triterpenoid MA in ameliorating DOX-induced cardiotoxicity and enhancing the antitumor efficacy of DOX., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)