A New Mechanism for Modulating the Activity of the Cancer Invasion Promoter Cyclooxase-2
Abstract
Cyclooxygenase-2 (COX-2) and its product PGE2 are known to promote tumor growth and to enhance the penetration of cancer cells into adjacent tissues. Thus, knowing how the activity of COX2 is regulated at the cellular level has implications for breast cancer therapeutic strategies. The goal is to unravel a new molecular mechanism for regulating the activity of COX-2. In plasma membranes, arachidonic acid (AA) is released by phospholipase A2 (PLA2). COX then converts AA to prostaglandins. The activity of PLA2 is known to vary with cholesterol content in an alternating manner, showing a local minimum at critical sterol mole fractions for maximal superlattice formation. In this study, the cholesterol content in MCF-7 human breast cancer cells was depleted by using methyl-beta-cyclodextrin. A biphasic change in COX-2 activity was observed at certain cell cholesterol content Cr. The cholesterol content near Cr could serve as a fine-tuning mechanism to regulate COX-2 activity and PGE2 production, and consequently, cancer cell growth and metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA493736
Entities
People
- Parkson L. Chong
Organizations
- Temple University