Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent years, the incidence and mortality of prostate cancer have increased dramatically in China. At earlier stages, most diagnosed prostate cancers are responsive to androgen depletion treatment, yet, nearly all patients will eventually progress to metastatic androgen-independent prostate cancer (AIPC), which still has no effective therapeutic method or drug to deal with. 11'-Deoxyverticillin A (C42) belongs to the family of epipolythiodioxopiperazines (ETPs), an interesting class of fungal toxins that inhibit farnesyl transferase. Compounds holding such a property have been explored as putative anticancer agents. In this study, using PC3M cells, an AIPC cell line, we investigated the effect of the compound on apoptosis and explored the underlying mechanism. It revealed that C42 markedly enhanced the activity of caspase-3/7 and increased the accumulation of the cleaved PARP, all of which are the markers of apoptosis. It also revealed that C42 either decreased cell viability or inhibited the growth of PC3M cells. Moreover, we observed that the loss of cell viability and cell growth inhibition induced by C42 were both time- and dosage dependent. Taken together, we indicated that C42 can induce caspase-dependent apoptosis in AIPC cells, and the results presented here will broaden our knowledge about the molecular mechanisms by which C42 exerts its anticancer activity, and future work in this direction may provide valuable information in the development of these compounds into effective cancer therapeutic strategies against androgen-independent prostate cancer.
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PMID:[11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells]. 2266 13

Recurrent prostate cancer remains a major clinical challenge. The lysine specific demethylase-1 (LSD1/KDM1A), together with the JmjC domain-containing JMJD2A and JMJD2C proteins, have emerged as critical regulators of histone lysine methylation. The LSD1-JMJD2 complex functions as a transcriptional co-regulator of hormone activated androgen and estrogen receptors at specific gene promoters. LSD1 also regulates DNA methylation and p53 function. LSD1 is overexpressed in numerous cancers including prostate cancer through an unknown mechanism. We investigated expression of the LSD1 and JMJD2A in malignant human prostate specimens. We correlated LSD1 and JMJD2A expression with known mediators of prostate cancer progression: VEGF-A and cyclin A1. We show that elevated expression of LSD1, but not JMJD2A, correlates with prostate cancer recurrence and with increased VEGF-A expression. We show that functional depletion of LSD1 expression using siRNA in prostate cancer cells decreases VEGF-A and blocks androgen induced VEGF-A, PSA and Tmprss2 expression. We demonstrate that pharmacological inhibition of LSD1 reduces proliferation of both androgen dependent (LnCaP) and independent cell lines (LnCaP: C42, PC3). We show a direct mechanistic link between LSD1 over-expression and increased activity of pro-angiogenic pathways. New therapies targeting LSD1 activity should be useful in the treatment of hormone dependent and independent prostate cancer.
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PMID:The lysine specific demethylase-1 (LSD1/KDM1A) regulates VEGF-A expression in prostate cancer. 2338 57