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Microarray transcriptomic data from LNCaP cells treated with vehicle, 10 nM bufalin or 20 nM bufalin for 24 h

ABSTRACT: Microarray transcriptomic data from LNCaP cells treated with vehicle, 10 nM bufalin or 20 nM bufalin for 24 h

PROVIDER: PRJNA485639 | ENA |

REPOSITORIES: ENA

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Microarray transcriptomic data from LNCaP cells treated with vehicle, 10 nM bufalin or 20 nM bufalin for 24 h

Project description:Bufalin is a major cardiotonic compound in the traditional Chinese medicine Chanshu preparations of toad skin secretions. Cell culture studies have suggested anti-cancer potential involving multiple cellular processes including differentiation, apoptosis, senescence and angiogenesis. In prostate cancer (PCa) cell models, P53-dependent and independent caspase-mediated apoptosis and androgen receptor (AR) antagonism have been described for bufalin at micromolar concentrations. Since pharmacokinetic study in humans indicated single nanomolar bufalin was safely achievable in the peripheral circulation, we evaluated its cellular activity within range with the AR-positive, P53-wild type and PTEN-negative human LNCaP PCa cells in vitro. Our data show that bufalin induced caspase-mediated apoptosis at 10 nanomolar or higher exposure concentration with concomitant suppression of AR protein and its best known target prostate specific antigen (PSA) and steroid receptor co-activator 1 and 3 (SRC-1, SRC-3). Bufalin exposure induced protein abundance of P53 (not mRNA) and P21Cip1, G2 arrest and increased senescence-like phenotype (SA-galactosidase). Small interference RNA knocking down of P53 attenuated bufalin-induced senescence, whereas knocking down of P21Cip1 exacerbated bufalin-induced caspase-mediated apoptosis. In vivo, daily i.p. injection of bufalin (1.5 mg/kg body weight) for 9 weeks delayed LNCaP subcutaneous xenograft tumor growth in NSG SCID mice with a 67% decrease of final weight without affecting body weight. Tumors from bufalin-treated mice exhibited increased phospho-P53 and SA-galactosidase without detectable caspase-mediated apoptosis or suppression of AR and PSA. Our data suggest potential applications of bufalin in adjuvant therapy of PCa recurrence in patients or chemoprevention of prostate carcinogenesis, engaging a selective activation of P53-senescence.

2018-08-13 | GSE118261 | GEO

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Transcription profiling of human LNCaP cells Androgen-starved treated with gedunin and androgen, androgen alone, or vehicle alone for 24h

Project description:Gedunin is a natural product that affects LNCaP androgen-signalling by 24h; We used microarrays to detail the androgen-responsive program of gene expression affected by gedunin treatment at 24h Experiment Overall Design: LNCaP cells were grown to 50% confluency and deprived of androgen, and subsequently treated with gedunin plus androgen, androgen alone, or vehicle alone for 24h prior to direct Trizol lysis and RNA isolation

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