Astrakurkurone, a sesquiterpenoid from wild edible mushroom, targets liver cancer cells by modulating Bcl-2 family proteins

IUBMB Life. 2019 Jul;71(7):992-1002. doi: 10.1002/iub.2047. Epub 2019 Apr 12.

Abstract

Induction of apoptosis is the target of choice for modern chemotherapeutic treatment of cancer, where lack of potent "target-specific" drugs has led to extensive research on anticancer compounds from natural sources. In our study, we have used astrakurkurone, a triterpene isolated from wild edible mushroom, Astraeus hygrometricus. We have discussed the structure and stability of astrakurkurone employing single-crystal X-ray crystallography and studied its potential apoptogenicity in hepatocellular carcinoma (HCC) cells. Our experiments reveal that it is cytotoxic against the HCC cell lines (Hep 3B and Hep G2) at significantly low doses. Further investigations indicated that astrakurkurone acts by inducing apoptosis in the cells, disrupting mitochondrial membrane potential and inducing the expression of Bcl-2 family proteins, for example, Bax, and the downstream effector caspases 3 and 9. A molecular docking study also predicted direct interactions of the drug with antiapoptotic proteins Bcl-2 and Bcl-xL. Thus, astrakurkurone could become a valuable addition to the conventional repertoire of future anticancer drugs. © 2019 IUBMB Life, 1-11, 2019.

Keywords: B-cell lymphoma-2 (Bcl-2); B-cell lymphoma-2 (Bcl-2) family; apoptosis; astrakurkurone; hepatocellular carcinoma; mitochondrial apoptosis; mitochondrial membrane potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle
  • Cell Proliferation
  • Crystallography, X-Ray
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Models, Molecular
  • Molecular Docking Simulation
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes