Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells: relationship to free radicals and lipid peroxidation and its modulation by calmodulin antagonists.
Specific fatty acids such as linoleic acid (LA), gamma-linolenic acid (GLA), dihomo gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed cytotoxicity towards human cervical (HeLa) cells in vitro. Cyclo-oxygenase inhibitor, indomethacin; lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA); anti-oxidant, vitamin E; and calmodulin antagonists, trifluoperazine (TFP) and chlorpromazine (CPZ) blocked the cytotoxic action of these fatty acids. GLA-induced free radical generation and lipid peroxidation were also inhibited by indomethacin, NDGA, vitamin E, TFP and CPZ. Both indomethacin and NDGA also showed significant anti-oxidant property. These results suggest that fatty acid-induced cytotoxic action against HeLa cells is a free radical dependent process and that it can be modulated by calmodulin antagonists. These results are in contrast to those observed by us earlier with human breast cancer cells where in it was found that the tumoricidal action of fatty acids can be blocked by anti-oxidants but not by cyclo-oxygenase (CO) and lipoxygenase (LO) inhibitors. From these results it can be suggested that though free radicals are the mediators of the tumoricidal action of fatty acids, the mechanism of their production may be different in different types of tumor cells.
Sagar
P S
PS
Department of Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India.
Das
U N
UN
Koratkar
R
R
Ramesh
G
G
Padma
M
M
Kumar
G S
GS
D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002277:Carcinoma / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000633:toxicity*; D005260:Female; D005609:Free Radicals; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology
D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D013481:Superoxides