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K M Menon

Publications and source records attributed to K M Menon.

131 records · Page 8Linked to original sources
PubMedDate not supplied

Substituted pyridines: nonsteroidal inhibitors of human placental aromatase cytochrome P-450.

The binding to human placental aromatase cytochrome P-450 and resulting extent of inhibition was examined for pyridine, pyridines substituted at the 2-, 3-, or 4-positions with phenyl or benzoyl groups, and the nonpyridinic structural analogs biphenyl and benzophenone. Spectral binding studies with partially purified aromatase indicated that pyridine, 3- and 4-phenylpyridines, and 3- and 4-benzoylpyridines interact at the active site via ligation of the pyridinic nitrogen to heme iron, as judged by the type II difference spectra. The apparent dissociation constants for these compounds are 2.1, 0.11, 0.09, 2.6, and 0.27 mM, respectively. Biphenyl, benzophenone, and 2-benzoylpyridine show exclusively a hydrophobic interaction in the presence of the substrate, androst-4-ene-3,17-dione, to give reverse type I difference spectra, with apparent spectral dissociation constants of 0.14, 0.42, and 1.8 mM, respectively. 2-Phenylpyridine shows a unique spectrum, previously not observed with cytochrome P-450, that has components of both type I and type II spectra. As measured by tritium ion release from [1 beta-3H]androst-4-ene-3,17-dione, competitive inhibition of human microsomal aromatase activity was observed with pyridine, 2-, 3-, and 4-phenylpyridines, biphenyl, and benzophenone, with Ki values of 320, 62, 1.48, 0.36, 750, and 130 microM, respectively. In contrast, 2-, 3-, and 4-benzoylpyridines exhibited complex kinetic behavior from which inhibition constants could not be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatase Inhibitors↗
PubMedDate not supplied

Regulation of PTP1D mRNA by peptide growth factors in the human endometrial cell line HEC-1-A.

OBJECTIVE: To assess, in the human endometrial cell line HEC-1-A, the presence of protein tyrosine phosphatase 1D (PTP1D) and the possible regulation of its mRNA expression by mitogens such as forskolin (an agent that increases intracellular cyclic adenosine monophosphate [cAMP] levels), epidermal growth factor (EGF), and insulin-like growth factor-I (IGF-I). METHODS: Cells were grown to confluence and maintained in serum-free media for 24 hours before treatment. Cells were exposed to forskolin, EGF, and IGF-I for increasing time periods (0, 1, 3, 6, and 24 hours), and PTP1D mRNA expression was determined by Northern blot analysis. In addition, cells were incubated with increasing doses of forskolin (final concentrations: 1, 5, 10, 20, and 30 mumol/L) for 6 hours. RESULTS: When treated with the various mitogens, cells increased their stimulation of PTP1D mRNA expression in a time- and dose-dependent fashion. Specifically, forskolin, EGF, and IGF-I induced maximal mRNA expression at 6, 3, and 6 hours, respectively. Expression induced by forskolin, EGF, and IGF-I was five, three, and six times control levels, respectively. At a dose of 10 mumol/L, forskolin induced PTP1D mRNA expression almost two times higher than control values. CONCLUSION: These data suggest that in human endometrial carcinomas, cAMP, EGF, and IGF-I may regulate the expression of PTP1D mRNA, which may, in turn, play a role in uncontrolled cell proliferation and neoplastic transformation.

Adenocarcinoma↗