The nature compound dehydrocrenatidine exerts potent antihepatocellular carcinoma by destroying mitochondrial complexes in vitro and in vivo

Cumulative evidence indicates that mitochondria dysfunction plays an important role in tumour treatment. Given the limited efficacy and toxicity of current mitochondria-targeted drugs, research into effective mitochondria-targeted anticancer agents remains an irresistible general trend. In this study, it was found that dehydrocrenatidine (DEC), a beta-carbolin alkaloid isolated from Picrasma quassiodes, displays a promising growth inhibitory effect in vitro and in vivo by inducing apoptosis of hepatocellular carcinoma (HCC) cells. Mechanistically, we provided that the possible target of DEC against HCC cells was determined by isobaric labels for relative and absolute quantification assay and validated them using further experiments. The results suggested that DEC can target and regulate the function of mitochondrial complexes I, III and IV, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction to exert its anti-HCC effects. In addition, the combination of DEC and sorafenib showed a synergistic effect and was also associated with mitochondrial dysfunction. Importantly, DEC did not show significant toxicity in mice. This study provided a new insight into underlying mechanisms in DEC-treated HCC cells, suggesting that DEC might be a mitochondrial targeting lead compound.

Automated summary

Cumulative evidence suggests that the dysfunction of mitochondria plays a crucial role in tumor treatment. In this study, it was found that dehydrocrenatidine (DEC) exhibits a promising inhibitory effect on the growth of hepatocellular carcinoma (HCC) cells by inducing apoptosis. DEC targets and regulates the function of mitochondrial complexes, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction. The combination of DEC and sorafenib also shows a synergistic effect.