Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo.

Abstract

AIM:

To evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms.

METHODS:

The cell killing ability of DL111-IT was measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting.

RESULTS:

DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50% cell inhibition (IC50 value) was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50%. Flow cytometric analysis indicated that DL111-IT could cause G1 arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT.

CONCLUSION:

DL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

• Authors: Qiao-Jun He, Bo Yang, Yi-Jia Lou, Rui-Ying Fang
• Journal: Asian journal of andrology (Asian J Androl) Vol. 7 Issue 4 Pg. 389-93 (Dec 2005) ISSN: 1008-682X [Print] China
• PMID: 16281086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Immunosuppressive Agents
• Retinoblastoma Protein
• Triazoles
• Cyclin D1
• 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole
• Cyclin-Dependent Kinase 4

Topics

• Androgens (pharmacology)
• Animals
• Cell Division (drug effects)
• Cell Line, Tumor
• Cyclin D1 (metabolism)
• Cyclin-Dependent Kinase 4 (metabolism)
• Dose-Response Relationship, Drug
• Female
• G1 Phase (drug effects)
• Humans
• Immunosuppressive Agents (pharmacology)
• In Vitro Techniques
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Prostatic Neoplasms (drug therapy, pathology)
• Resting Phase, Cell Cycle (drug effects)
• Retinoblastoma Protein (metabolism)
• Transplantation, Heterologous
• Triazoles (pharmacology)