Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to the effects of estrogens on transcription, mediated by the estrogen receptor, and the antiestrogenic effects of triphenylethylene derivatives resulting from their competitive action at the estrogen receptor level, estrogens and antiestrogens can affect cellular processes though other mechanisms. Estrogens can bind and alter enzymatic activities in membranes isolated from target cells, can influence the activities of purified enzymes and can change cell permeability and polarization under conditions excluding transcriptional effects. Triphenylethylene antiestrogens at micromolar concentrations can affect cholinergic, histaminergic and dopaminergic systems, affect calmodulin action and influence protein kinase C activity. Tamoxifen added to suspension of human endometrial adenocarcinoma cells at concentrations greater than 10 microM both increased phosphoinositide hydrolysis and inhibited the stimulatory effect of carbachol on this system. These effects, however, may represent nonspecific actions of the antiestrogens, shared with the structurally related phenothiazines, on the plasma membrane.
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PMID:Non-genomic effects of estrogens and antiestrogens. 284 81

The antitumoral activity of non-steroidal antiestrogens on promyelocytic leukemia HL60 and T lymphoblastic MOLT3 cell lines was studied. Tamoxifen and its derivatives, clomiphene and nafoxidine, caused reduction of cell viability in a dose-dependent manner. These drugs showed differences in their potency following four days incubation, with nafoxidine being the most efficient inhibitor and tamoxifen the least active. Apoptosis was induced as assessed by the DNA ladder pattern and formation of pre G0/G1 population as detected by flow cytometry analysis of DNA. The effect of these drugs was abrogated by antioxidants: alpha-tocopherol was most effective in antagonizing the drugs' effect. N-acetyl L-cysteine reversed mainly the decrease in cell viability caused by the drugs, but was less active on induction of apoptosis. GF109203X, a protein kinase inhibitor, attenuated apoptosis induced by clomiphene in MOLT3 cells. The results suggest that the antileukemic activity of the antiestrogens is mediated by oxidative stress and protein kinase C (PKC) activation. Triphenylethylene antiestrogens and their derivatives may be used as antileukemic drugs which kill cells by apoptosis mediated by oxidative stress and activation of PKC.
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PMID:Non-steroidal antiestrogens induce apoptosis in HL60 and MOLT3 leukemic cells; involvement of reactive oxygen radicals and protein kinase C. 1047 Jan 53