Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 microM of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis.
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PMID:Polycyclic aromatic hydrocarbon-induced CYP1B1 activity is suppressed by perillyl alcohol in MCF-7 cells. 1630 65

We previously demonstrated in prostate cancer cells that a phytochemical-perillyl alcohol-and the mechanistic target of rapamycin (mTOR) inhibitor rapamycin rapidly attenuated telomerase activity. Protein levels of the telomerase catalytic subunit reverse transcriptase (hTERT) were diminished in the absence of an effect on hTERT mRNA, supporting an effect on 4E-BP1 phosphorylation and reduced initiation of protein translation. The decline in hTERT protein did not coincide wholly, however, with loss of telomerase activity suggesting a further level of regulation. We hypothesized that a hTERT-mTOR-S6K (S6 kinase)-Hsp90 (Heat shock protein 90)-Akt complex previously detected in activated NK cells was present in DU145 prostate cancer cells. Furthermore, we postulated that both perillyl alcohol and rapamycin disrupted this complex to control telomerase activity post-translationally. Antibodies directed against either RAPTOR, a binding partner of mTOR, or mTOR itself co-immunoprecipitated Hsp90, hTERT, and S6K confirming a similar TERT complex in prostate cancer cells. Perillyl alcohol or rapamycin caused rapid dissociation of the captured hTERT-mTOR-RAPTOR complex, establishing an additional mechanism by which these agents decrease telomerase activity. These findings provide convincing evidence for mTOR-mediated regulation of hTERT in DU145 cells.
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PMID:Disruption of an hTERT-mTOR-RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin. 2328 42