Cytotoxic effects of cigarette smoke alkaloids inhibit the progesterone production and cell growth of cultured MA-10 Leydig tumor cells.
Inhibition of corpus luteum progesterone synthesis by cigarette smoke alkaloids might, in part, explain the generally poorer outcome of pregnancy in smoking women. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone biosynthesis and cell growth. Studies were based using the MA-10 Leydig tumor cell line. The steroid pathway in MA-10 cells has only two specific enzymatic steps. The cholesterol passes to the cholesterol side-chain cleavage enzyme and then metabolizes the resulting pregnenolone to progesterone and partly to 20alpha-dihydroprogesterone. Incubation of MA-10 cells with nicotine, cotinine, anabasine, all of these alkaloids, or an aqueous extract of cigarette smoke resulted in dose-dependent inhibition of progesterone and 20alpha-dihydroprogesterone synthesis. The number of cells in the treated dishes seemed less than the control. This latter finding prompted experiments evaluating the short-term effects of the alkaloids on cell growth. Growth of MA-10 cells influenced with alkaloids or smoke extract was also inhibited. All of the inhibitory effects of nicotine, cotinine, anabasine and cigarette smoke extract on MA-10 cells were explained by cytotoxicity. The cytotoxic effect could reduce the fertilization, implantation, and early human development. This mechanism entails the consequence of impaired placental growth, disorder in the placental vascular architecture and placental circulation, and small-for-date babies.
Gocze
P M
PM
Department of Obstetrics and Gynecology, Pecs University Medical School, Edesanyak utja 17, H-7624, Pecs, Hungary.
Freeman
D A
DA
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis; D000470:Alkaloids / Q000494:pharmacology*; D000691:Anabasine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism; D003367:Cotinine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007984:Leydig Cell Tumor / Q000378:metabolism* / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology; D010051:Ovarian Neoplasms; D010947:Plants, Toxic; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D012906:Smoke / Q000032:analysis*; D014026:Nicotiana; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D012906:Smoke; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D009538:Nicotine; D011284:Pregnenolone; D004247:DNA; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003367:Cotinine; D000691:Anabasine