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

Mol Med Rep. 2022 Jan;25(1):34. doi: 10.3892/mmr.2021.12550. Epub 2021 Dec 1.

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.

Keywords: acute myeloid leukemia; apoptosis; autophagy; corilagin; high mobility group protein B1; miR‑451.

MeSH terms

  • Apoptosis*
  • Autophagy*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glucosides / pharmacology*
  • HL-60 Cells
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Hydrolyzable Tannins / pharmacology*
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • MicroRNAs / genetics*

Substances

  • Glucosides
  • HMGB1 Protein
  • HMGB1 protein, human
  • Hydrolyzable Tannins
  • MIRN451 microRNA, human
  • MicroRNAs
  • corilagin

Grants and funding

The present study was supported by the Science and Technology Development Program of Medical and Health from Shandong Province (grant no. 2018WSB34003), PhD Research Foundation of Affiliated Hospital of Jining Medical University (grant no. 2018-BS-011) and Incubation Project of National Natural Science Foundation of China (grant no. 700103005).