Autophagy is a pro-survival mechanism in ovarian cancer against the apoptotic effects of euxanthone.
Paraules clau
Resum
BACKGROUND
Ovarian cancer is one of the most prevalent gynecological malignancies and thus the development of novel therapeutic agents for managing ovarian cancer is imperative. Euxanthone, a xanthone derived from Polygala caudata, has been found to exert cytotoxic effects on cancerous cells. This study was designed to assess the role of euxanthone in ovarian cancer.
METHODS
Cell Counting Kit-8 (CCK-8) assay was utilized to assess the viability of human ovarian cancer SKOV3 and OVCAR3 cell lines. The population of apoptotic cells was measured by flow cytometry and TUNEL assay. Cell cycle analysis was carried out by flow cytometry. Autophagy was determined by western blotting to detect LC3-II, p62 degradation, and Beclin1 expression, by transfection with GFP-LC3B expressing plasmid and by flow cytometry. To examine the role of STAT3 in the induction of autophagy and apoptosis by euxanthone, STAT3 expression was suppressed using siRNA. Moreover, xenograft model was established to evaluate the therapeutic effect of euxanthone in vivo.
RESULTS
Euxanthone decreased cell viability and blocked cell cycle progression at G2/M phase. Euxanthone induced apoptotic cell death in a caspase-dependent manner in ovarian cancer cells. Euxanthone treatment also led to the accumulation of autophagosomes. We also found that inhibition of autophagy by 3-MA or Beclin1 siRNA enhanced the pro-apoptotic effect of euxanthonein ovarian cancer cells. Furthermore, our results revealed that euxanthone induced apoptosis and autophagy by modulating pSTAT3/Bcl-2 signaling. In vivo data also demonstrated that euxanthone exerted anti-tumor activities without harming healthy tissues.
CONCLUSIONS
Euxanthone induced cytoprotective autophagy in ovarian cancer cells, which negatively contributed to its anti-tumor activities. Our findings provide preliminary experimental data that support further investigation on the therapeutic efficacy of euxanthone in ovarian cancer.
