HO-3867, a curcumin analog, elicits cell apoptosis and p38-mediated caspase activation in hepatocellular carcinoma

Environ Toxicol. 2024 Feb;39(2):794-802. doi: 10.1002/tox.23977. Epub 2023 Oct 2.

Abstract

HO-3867, a synthetic curcumin analog, has displayed various tumor-suppressive characteristics and improved bioabsorption over its parent compound. However, its influences on the development of hepatocellular carcinoma (HCC) are poorly defined. To address this, we tested the anticarcinogenic impact of HO-3867 and investigated the underlying mechanisms in fighting liver cancer. Our result demonstrated that HO-3867 reduced the viability of HCC cells, accompanied by promotion of cell cycle arrest at the sub-G1 stage and apoptotic responses. Furthermore, a distinctive profile of apoptosis associated proteins, encompassing elevated heme oxygenase-1 (HO-1) level and caspase activation, was detected in HO-3867-stimulated HCC cells. In addition, such HO-3867-mediated elevation in caspase activation was dampened by pharmacological suppression of p38 activities. Taken together, our findings unveiled that HO-3867 triggered cell cycle arrest and apoptotic events in liver cancer, involving a p38-mediated activation of caspase cascades. These data highlighted a usefulness of curcumin or its analogs on the management of hepatocarcinogenesis.

Keywords: HO-3867; apoptosis; curcumin; hepatocellular carcinoma; p38.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular* / pathology
  • Caspase 3 / metabolism
  • Caspases
  • Cell Line, Tumor
  • Curcumin* / pharmacology
  • Heme Oxygenase-1
  • Humans
  • Liver Neoplasms*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Curcumin
  • (3,5-bis((4-fluorophenyl)methylidene)-1-((1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl)piperidin-4-one)
  • Heme Oxygenase-1
  • Caspases
  • Caspase 3
  • p38 Mitogen-Activated Protein Kinases