Proscillaridin A inhibits hepatocellular carcinoma progression through inducing mitochondrial damage and autophagy

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. At present, drug options for systemic treatment of HCC are very limited. There is an urgent need to develop additional effective drugs for HCC treatment. In the present study, we found that proscillaridin A (ProA), a cardiac glycoside, exerted a strong anticancer effect on multiple HCC cell lines. ProA significantly inhibited the cell proliferation, migration, and invasion of HCC cells. ProA also had a marked inhibitory effect on the progression of HCC in the MHCC97H xenograft nude mouse model. ProA-mediated suppression of HCC was closely related to cell apoptosis. ProA-treated HCC cells displayed significant mitochondrial damage and elevated reactive oxygen species production, resulting in profound cell apoptosis. Meanwhile, ProA also played a role in autophagy induction in HCC cells. Defects in autophagy partially relieved ProA’s anticancer effect in HCC cells. Our findings demonstrate that ProA can effectively inhibit HCC progression and may serve as a potential therapeutic agent for HCC treatment.

Knockdown of FAM225B inhibits the progression of the hypertrophic scar following glaucoma surgery by inhibiting autophagy

“…Based on these aforementioned findings, it can be concluded that knockdown of FAM225B induced cell injury and increased the oxidative stress of scar fibroblasts by inhibiting cell autophagy and inducing apoptosis. Moreover, a previous study reported that Proscillaridin A could induce apoptosis and autophagy in liver cancer cells ( 43 ). Thus, the association between apoptosis and autophagy requires further investigation.…”

“…Apoptosis is closely associated with autophagy in types of cancer, including hepatocellular carcinoma ( 43 , 44 ). Importantly, autophagy is necessary for the onset of apoptosis, which usually triggers the occurrence of cell apoptosis and injury ( 45 , 46 ).…”

Cardiac Glycosides as Autophagy Modulators

“…In hepatocellular carcinoma cell lines, proscillaridin A (10 to 500 nM, 48 h) causes mitochondrial damage as observed by transmission microscopy, which happens due to ROS formation. Fifty nM of proscillaridin A induces autophagy in human cells derived from hepatocarcinoma (MHCC97H, and Huh7) after 24 h of treatment (LC3-II increase, inhibition of mTOR) [ 111 ]. As confirmed by Saleem et al [ 112 ], proscillaridin A could be combined with autophagy inhibitors to increase its anticancer potential.…”

Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells

“…In cardiomyocytes, Pro A binds and inhibits Na + /K + -ATPase, resulting in enhanced myocardial contraction ( 19 ). Pro A has shown anti-tumor effects on various cancers, including breast cancer ( 20 ), prostate cancer ( 21 ), hepatocellular carcinoma ( 22 ), leukemia ( 23 ) and non-small cell lung cancer ( 24 ). Pro A has also been demonstrated to inhibit PC cells at micro-molar concentrations using 3D spheroid cultures ( 25 ).…”