Abstract
Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anticancer effects against a broad spectrum of tumors. In an in vivo experiment, we found that apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2, combined with elemene injection (Ele) for the treatment of H22 solid tumor in mice resulted in worse effectiveness than apatinib alone. Moreover, Ele could protect HepG2 cells from death induced by serum-free starvation. Further data on the mechanism study revealed that Ele induced protective autophagy and prevented human hepatoma cancer cells from undergoing apoptosis. Proapoptosis effect of Ele was enhanced when proautophagy effect was inhibited by hydroxychloroquine. Above all, Ele has the effect of protecting cancer cells from death either in apatinib induced nutrient deficient environment or in serum-free induced starvation. A combination of elemene injection with autophagy inhibitor might thus be a useful therapeutic option for hepatocellular carcinoma.
Highlights
Primary liver cancer is the most common malignant tumor, which accounts for 45% of the global incidence of the morbidity and mortality rates are in the second tumor spectrum
The results revealed that Ele elemene injection induced autophagy protects human hepatoma cancer cells from starvation and undergoing apoptosis
Hepatocellular carcinoma (HCC) represents the major histological subtype accounting for 70% to 85% of the total liver cancer burden worldwide [8]
Summary
Primary liver cancer is the most common malignant tumor, which accounts for 45% of the global incidence of the morbidity and mortality rates are in the second tumor spectrum. Hepatocellular carcinoma (HCC), a primary liver cancer, is the most common type accounting for 90% of primary liver cancer. In vivo and in vitro experiments confirmed elemene injection (Ele) has good induction of apoptosis and antiangiogenic effects on a variety of tumor cells [1, 2]. We found elemene injection had both proapoptotic and proautophagic effect on human hepatoma cell line HepG2. Since autophagy can result in both survival and cell death, we asked whether Ele-induced autophagy is protective or proapoptotic. The results revealed that Ele elemene injection induced autophagy protects human hepatoma cancer cells from starvation and undergoing apoptosis
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