Effects of high-dose medroxyprogesterone acetate and various other steroid hormones on plasma membrane lipid mobility in CAMA-1 mammary cancer cells.

Abstract

The influence of medroxyprogesterone acetate (MPA) and various other steroid hormones on the lateral diffusion of the fluorescent lipid probe 1-acyl-2-(N-4-nitrobenzo-2-oxa-1.3-diazolyl)-aminocarpropylphos phatidylcholine (NBD-PC) in the plasma membrane of intact mammary cancer cells (CAMA-1 cell line) has been studied by fluorescence recovery after photobleaching technique. Incubation of cells with MPA in serum free medium at ambient temperature for 1 hr led to a significant decrease in the lateral diffusion coefficient of NBD-PC. MPA induced this change over a limited concentration range with 10(-7)-10(-5) mol/l near-maximal or maximal effects, and 10(-8) mol/l exhibiting no effect. Exposure of the CAMA-1 cells to 10(-7) mol/l MPA in undiluted serum induced a significant effect following 1.5 hr of treatment with no increase in effectiveness up to 4 hr of incubation. As compared to MPA, the other steroids tested were less effective or ineffective. The influence on lateral lipid mobility diminished as follows: MPA greater than progesterone greater than 5a-DHT approximately 17 beta-estradiol greater than dexamethasone, and roughly seems to parallel their lipid solubility as estimated by partition coefficients in an n-octanol-water system. Any involvement of classical steroid hormone receptors in the mechanism of membrane action could be excluded. Nongenomic steroid effects on the plasma membrane are assumed. As the structure and function of biomembranes are modulated by lipid-bilayer fluidity and membranes crucially participate in nearly all aspects of cell biology, it is concluded that direct interactions of MPA with membranes potentially play a role in the antitumor activity of the compound.

• Authors: T Van Bömmel, T Marsen, H Bojar
• Journal: Anticancer research (Anticancer Res) 1987 Nov-Dec Vol. 7 Issue 6 Pg. 1217-23 ISSN: 0250-7005 [Print] Greece
• PMID: 2964808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Lipids
• Steroids
• Dihydrotestosterone
• Progesterone
• Estradiol
• Dexamethasone
• Medroxyprogesterone Acetate
• Medroxyprogesterone

Topics

• Algorithms
• Animals
• Cell Membrane (drug effects, metabolism)
• Dexamethasone (pharmacology)
• Diffusion
• Dihydrotestosterone (pharmacology)
• Estradiol (pharmacology)
• Mammary Neoplasms, Experimental (metabolism, ultrastructure)
• Medroxyprogesterone (administration & dosage, analogs & derivatives, pharmacology)
• Medroxyprogesterone Acetate
• Membrane Fluidity (drug effects)
• Membrane Lipids (metabolism)
• Progesterone (pharmacology)
• Steroids (administration & dosage, pharmacology)
• Tumor Cells, Cultured (drug effects, ultrastructure)