Discovery of β-cyclocitral-derived mono-carbonyl curcumin analogs as anti-hepatocellular carcinoma agents via suppression of MAPK signaling pathway

Bioorg Chem. 2023 Mar:132:106358. doi: 10.1016/j.bioorg.2023.106358. Epub 2023 Jan 10.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high recurrence and mortality rate. In this study, a series of β-cyclocitral-derived mono-carbonyl curcumin analogs were synthesized and their anticancer properties were evaluated. Among the series, A19 exhibited the strongest cytotoxic activity by inhibiting cell viability and colony formation, inducing cell cycle G2/M phase arrest and cell apoptosis of HCC HepG2 and Huh-7 cells, while having almost no cytotoxicity on normal liver MIHA cells. Mechanistically, our results demonstrated that A19 triggered intense DNA damage via suppression of the ERK/JNK/p38 MAPK signaling pathway. Additionally, a combination of A19 with sorafenib significantly induced synergistic cytotoxicity in HCC cells. Overall, our results indicate the potential of A19 as a novel chemotherapeutic drug administered either separately or in combined therapy for HCC treatment.

Keywords: DNA damage; Hepatocellular carcinoma; MAPK signaling pathway; Mono-carbonyl curcumin analogs; β-cyclocitral.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms* / pathology
  • Signal Transduction

Substances

  • Curcumin
  • beta-cyclocitral
  • Antineoplastic Agents