Competitive inhibition of human placental aromatase by N-n-octanoylnornicotine and other nornicotine derivatives.
In a study of the effect of N-n-octanoylnornicotine and other acyl derivatives of nornicotine on the aromatization of androstenedione by human placental microsomal aromatase, we found that N-n-octanoylnornicotine, a component of cigarette smoke, exhibited competitive inhibition with an apparent Ki of 0.65 microM. This is comparable to that of aminoglutethimide, the clinically-used non-steroidal aromatase inhibitor. N-n-Decanoylnornicotine and N-(4-hydroxyundecanoyl)nornicotine exhibited apparent Ki values of 0.86 microM and 0.24 microM, respectively. This study suggests that cigarette smoke components may have a direct effect on estrogen biosynthesis and that these compounds may prove to be useful parent structures for development of active site probes for further elucidation of estrogen biosynthesis and might eventually lead to the development of alternative non-steroidal anti-cancer therapy.
Bullion
K
K
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
Ohnishi
S
S
Osawa
Y
Y
D000735:Androstenedione / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001667:Binding, Competitive / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology*; D012907:Smoking / Q000009:adverse effects*; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; C074420:N-octanoylnornicotine; D000735:Androstenedione; D009538:Nicotine; C005311:nornicotine