Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression.

Abstract

PURPOSE:

Ovarian cancer is the leading cause of death among all gynecological malignancies in Western countries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed significantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of effective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and discovering effective novel drugs with different molecular structures from conventional chemotherapy agents have become an urgent clinical need.

METHODS:

Ovarian cancer cells were treated with lovastatin and atorvastatin. Apoptosis in these cells and tumor formation in soft agar were determined. The molecular mechanism by which statins suppress ovarian cancer cell growth was evaluated.

RESULTS:

Both lovastatin and atorvastatin effectively induced apoptosis in ovarian cancer cells and suppressed anchorage-independent growth of these cells in soft agar. Further investigation of the molecular mechanism has revealed that the expression of Cdc42 and Rac1, small GTPase family members, was highly induced in the cells by these statins along with the activation of Jun N-terminal kinases (JNK). In addition, Bim, a proapoptotic protein, was significantly induced by these statins.

CONCLUSIONS:

Our findings provide new insight into the molecular mechanism by which statins induce apoptosis in ovarian cancer cells and may lead to novel therapies for advanced ovarian cancer.

• Authors: Hongli Liu, Shu-Ling Liang, Sheetal Kumar, Crystal M Weyman, Wendy Liu, Aimin Zhou
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 63 Issue 6 Pg. 997-1005 (May 2009) ISSN: 1432-0843 [Electronic] Germany
• PMID: 18766339 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• BCL2L11 protein, human
• Bcl-2-Like Protein 11
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Membrane Proteins
• Proto-Oncogene Proteins
• Pyrroles
• RAC1 protein, human
• Lovastatin
• Atorvastatin
• JNK Mitogen-Activated Protein Kinases
• cdc42 GTP-Binding Protein
• rac1 GTP-Binding Protein

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (biosynthesis)
• Atorvastatin
• Bcl-2-Like Protein 11
• Cell Culture Techniques
• Cell Line, Tumor
• Cell Survival (drug effects)
• Female
• Heptanoic Acids (pharmacology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lovastatin (pharmacology)
• Membrane Proteins (biosynthesis)
• Ovarian Neoplasms (enzymology, metabolism, pathology)
• Proto-Oncogene Proteins (biosynthesis)
• Pyrroles (pharmacology)
• cdc42 GTP-Binding Protein (biosynthesis)
• rac1 GTP-Binding Protein (biosynthesis)