CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells

Hae Yun Jung, Sun Hee Park, Young Do Yoo, Jun Suk Kim, Yeul Hong Kim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Retinoic acid (RA) is an important regulator of normal cellular proliferation and differentiation and suppressor of tumor growth by cell cycle arrest and apoptosis. Furthermore, RA showed a chemo-preventive activity in preclinical and/or clinical models of lung, head and neck, breast, and hepatocellular carcinoma (HCC). In this study, we examined the effect of RA on the proliferation of human HCC cells, in order to analyze its mode of action and, finally, we attempted to find a surrogate biomarker of RA for HCC chemopreventive treatment. Our findings suggested that the growth inhibition of RA in HCC cells differed according to G1 phase delay by CDK2 or 4, finally induction of apoptosis. No correlation was found between RA sensitivity and the expression of nuclear retinoid receptors, such as RARs or RXRs in HCC cells. RA treatment caused cell cycle arrest at G1 and decreased the expressions and activities of CDK2 or CDK4 in RA-sensitive HepG2 and SNU354 cells. On the other hand, RA-resistant Hep3B and SNU449 cells progressed into the S/G2 + M phase and showed increased CDK2 and CDK4 expression and activity. Since the inhibition of CDK2 or 4 activities resulted in sensitization of HCC cells to RA, the combination of RA and compounds of inhibiting CDKs such as UCN01 and flavopiridol might be a useful targeted therapy strategy for HCC.

Original languageEnglish
Pages (from-to)143-152
Number of pages10
JournalHepatology Research
Issue number3
Publication statusPublished - 2005 Mar


  • Anti-cancer agent
  • CDK2
  • CDK4
  • Hepatocellular carcinoma
  • Retinoic acid

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases


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