Corilagin induces apoptosis and inhibits autophagy of HL‑60 cells by regulating miR‑451/HMGB1 axis.

Abstract

Corilagin is the primary active component of the Euphorbia phyllanthus plant and has significant anti-cancer properties. However, the biological effects and mechanisms of corilagin on acute myeloid leukemia (AML) have not been clarified. The Cell Counting Kit-8 and Carboxyfluorescein Diacetate Succinimidyl Ester assay results showed that corilagin significantly inhibited proliferation of the AML cell line HL-60 in a time- and dose-dependent manner. Western blotting and flow cytometry analysis were performed to determine the levels of apoptosis in HL-60 cells. The protein levels of cleaved caspase-3 and Bak were upregulated, while Bcl-xl was downregulated in cells treated with corilagin. The percentage of early- and late-stage apoptotic cells increased following corilagin treatment in a dose-dependent manner, indicating that the intrinsic mitochondrial apoptosis pathway was activated by corilagin. Simultaneously, western blotting and immunofluorescence results revealed that autophagy was suppressed; this was accompanied by a decrease in light chain 3-II (LC3-II) conversion and autophagosomes. MicroRNA (miRNA/miR) profile analysis showed that corilagin elevated the expression of the tumor suppressor miR-451, while the mRNA and protein levels of high mobility group protein B1 (HMGB1), the target of miR-451, decreased following exposure to corilagin. Knockdown of miR-451 decreased the downregulation of HMGB1 caused by corilagin, indicating negative regulation of HMGB1 by miR-451 during corilagin treatment. Furthermore, knockdown of miR-451 also attenuated corilagin-induced proliferation inhibition of HL-60 cells, implying that miR-451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL-60 cells by regulating the miR-451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.