Droloxifene (3-hydroxytamoxifen) has membrane antioxidant ability: potential relevance to its mechanism of therapeutic action in breast cancer.
Droloxifene (3-hydroxytamoxifen), is a triphenylethylene derivative recently developed for the treatment of breast cancer. Droloxifene was found to exhibit a membrane antioxidant ability in that it inhibited Fe(III)-ascorbate dependent lipid peroxidation in rat liver microsomes and ox-brain phospholipid liposomes. It also inhibited microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH. Droloxifene was a better inhibitor of lipid peroxidation than tamoxifen, but was less effective than 17 beta-oestradiol in the two microsomal systems and in the preformed liposomal system. When introduced into ox-brain phospholipid liposomes, droloxifene inhibited Fe(III)-ascorbate induced lipid peroxidation to approximately the same extent as similarly introduced cholesterol and tamoxifen, although to a lesser extent than 17 beta-oestradiol. This inhibition of lipid peroxidation by droloxifene may result from a membrane stabilization that could be associated in cancer cells with decreased plasma membrane fluidity. This mechanism may be related to the clinically important antiproliferative action of droloxifene on cancer cells.
Wiseman
H
H
Department of Biochemistry, King's College London, UK.
Smith
C
C
Halliwell
B
B
Cannon
M
M
Arnstein
H R
HR
Lennard
M S
MS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D000975:Antioxidants; D008081:Liposomes; D013629:Tamoxifen; C038345:droloxifene; D004958:Estradiol; D007501:Iron