Growth inhibition of gastric cancer cells by all-trans retinoic acid through arresting cell cycle progression.

Abstract

OBJECTIVE:

To investigate the mechanism of all-trans retinoic acid (ATRA) on the regulation of the cell cycle in gastric cancer cells.

METHODS:

The protein level was detected by Western blot. Immunoprecipitation was used in protein kinase activity determination. Cell growth and cell cycle phase were examined by MTT assay and flow-cytometric analysis, respectively.

RESULTS:

ATRA could effectively induce G0/G1 arrest and inhibit cell growth in certain human gastric cancer cell lines. ATRA might induce p21WAF1/CIP1 expression in ATRA-sensitive cell lines through p53-dependent and p53-independent pathways. Induction of p21WAF1/CIP1 caused decrease in CDK4 and CDK2 activities independent of CDK4 and CDK2 protein expression levels. In addition, the dephosphorylated form of Rb protein increased because of the down-regulation of CDK4 and CDK2 activities by ATRA.

CONCLUSIONS:

Growth inhibition on gastric cancer cells by ATRA occurs through the regulation of relevant proteins leading to the arrest of cell cycle progression.

• Authors: Q Wu, Z Chen, W Su
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 114 Issue 9 Pg. 958-61 (Sep 2001) ISSN: 0366-6999 [Print] China
• PMID: 11780391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin E
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• Tretinoin

Topics

• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Cell Cycle (drug effects, physiology)
• Cell Division (drug effects)
• Cyclin E (drug effects, metabolism)
• Cyclin-Dependent Kinase Inhibitor p16 (drug effects, metabolism)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Humans
• Phosphorylation (drug effects)
• Retinoblastoma Protein (drug effects, metabolism)
• Stomach Neoplasms (drug therapy, pathology, physiopathology)
• Time Factors
• Tretinoin (pharmacology)
• Tumor Cells, Cultured (drug effects, metabolism)
• Tumor Suppressor Protein p53 (drug effects, metabolism)