Hydroxysafflor yellow A promotes apoptosis via blocking autophagic flux in liver cancer

Hydroxysafflor yellow A (HSYA) extracted from the herb Cathartics tinctorius L. negatively regulates liver cancer growth. However, the exact mechanism of HSYA action in liver cancer remains largely unknown. In this study, HSYA inhibited liver cancer cell growth in vivo and in vitro, evidenced by cell proliferation inhibition detected by CCK8, numerous apoptotic cells shown by flow cytometry assay, and expression of apoptosis-related proteins determined by western blot. Importantly, our data revealed that HSYA triggered autophagic response and autophagosome accumulation considering the increased levels of LC3II-conversion examined by western blot, LC3 puncta visualized by immunofluorescence, and expression of autophagy-related genes shown by quantitative real-time PCR. Furthermore, HSYA blocked the late-phase of autophagic flux via impairing the lysosomal acidification and downregulating LAMP1 expression, thereby likely inducing apoptosis. In addition, HSYA inhibited PI3K/AKT/mTOR signaling pathway. Taken together, as HSYA might inhibit cell proliferation and promote apoptosis via blocking autophagic flux in liver cancer, it may be considered a promising candidate for liver cancer therapy.