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Curcumol Induces G1 Phase Arrest in SK-Hep-1 Cells by Targeting SKP2-Mediated p27 Degradation

Yizhuang Yang1, Riqiu Zhang2, Tong Dou1,3

  • 1Department of Pharmacy, Guilin Medical University, Zhiyuan Road, Lingui, Guilin 541199, China.

Molecules (Basel, Switzerland)
|March 28, 2026
PubMed
Abstract

Insights

Curcumol halts cancer cell growth by reducing S-phase kinase-associated protein 2 (SKP2) expression, inhibiting p27 degradation, and causing cell cycle arrest. Overexpressing SKP2 partially reverses these effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • S-phase kinase-associated protein 2 (SKP2) is a key oncogene and cell cycle regulator.
  • Curcumol, a natural product, shows potential in overcoming drug resistance by modulating SKP2-mediated ubiquitination.
  • The precise role of SKP2 in curcumol's cell cycle arrest mechanism remains largely unexplored.

Purpose of the Study:

  • To elucidate the role of SKP2 in curcumol-induced G1 phase cell cycle arrest.
  • To investigate the molecular mechanisms underlying curcumol's effects on SKP2 and its interacting proteins.

Main Methods:

  • Transcriptomic and proteomic analyses identified ubiquitination-related factors in curcumol-treated hepatocellular carcinoma cells.
  • Lentiviral overexpression, co-immunoprecipitation, and ubiquitination assays were employed to study SKP2 function.
  • Cell-line-derived xenograft (CDX) models were used for in vivo validation.

Main Results:

  • Curcumol modulated key cell cycle regulators including CDK4, CDK6, Cyclin D1, p27, and SKP2.
  • SKP2 overexpression partially reversed curcumol's anti-proliferative and G1 arrest effects.
  • Curcumol inhibited the SKP2-p27 interaction, leading to decreased p27 ubiquitination and degradation.

Conclusions:

  • Curcumol induces G1 phase cell cycle arrest by reducing SKP2 expression and inhibiting p27 degradation.
  • The findings highlight a novel mechanism of curcumol's action involving the SKP2/p27 axis.
  • Targeting SKP2 may enhance the efficacy of curcumol as an anti-cancer therapeutic.
Keywords:
SKP2cell cyclecurcumolhepatocellular carcinomap27

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