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

Hae Y. Jung, Sun H. Park, Young Do Yoo, Jun Suk Kim, Yeul Hong Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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
Volume31
Issue number3
DOIs
Publication statusPublished - 2005 Mar 1

Fingerprint

Tretinoin
Hepatocellular Carcinoma
alvocidib
Apoptosis
G1 Phase Cell Cycle Checkpoints
G2 Phase
Retinoids
Hep G2 Cells
G1 Phase
Cytoplasmic and Nuclear Receptors
Growth
Cell Cycle Checkpoints
Cell Division
Neck
Biomarkers
Head
Cell Proliferation
Breast Neoplasms
Lung

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells. / Jung, Hae Y.; Park, Sun H.; Yoo, Young Do; Kim, Jun Suk; Kim, Yeul Hong.

In: Hepatology Research, Vol. 31, No. 3, 01.03.2005, p. 143-152.

Research output: Contribution to journalArticle

Jung, Hae Y. ; Park, Sun H. ; Yoo, Young Do ; Kim, Jun Suk ; Kim, Yeul Hong. / CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma cells. In: Hepatology Research. 2005 ; Vol. 31, No. 3. pp. 143-152.
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