Naslov
The effect of a phospholipase C gamma inhibitor on the proliferation and phenotype of Du145 prostate cancer cells

Autori
Režić-Mužinić, Nikolina ; Mastelić, Angela ; Markotić, Anita ; Čikeš Čulić, Vedrana ; Vuica- Ross, Milena ; Ross, Ashley ; Barker, David ; Reynisson, Jóhannes

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
FEBS J 281(Suppl. 1) / - , 2014, 507-507

Skup
FEBS EMBO 2014 Conference

Mjesto i datum
Pariz, Francuska, 30.08.2014. - 04.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
prostate cancer ; phospholipase C inhibitor

Sažetak
INTRODUCTION: Prostate cancer remains the second most common cause of cancer related death among men, highlighting the need for new therapies. Many cancer cellular functions have been discovered to be regulated by phospholipase C (PLC) gamma activation, suggesting that it represents an important therapeutic target for development of anticancer drugs. Here, we investigate the influence of a newly developed, small molecule PLC gamma inhibitor, with or without taxane therapy, on the growth and survival of sub-populations of a prostate cancer cell line. MATERIALS AND METHODS: Cells were incubated 48h with Paclitaxel (5 nM) and PLC gamma inhibitor (1 microM) alone or in their combination.The viable cells were determined by the MTT assay. Flow cytometric analysis of cells positive to anti- CD44, anti-CD54, and propidium iodide staining was performed to characterise apoptotic Du145 sub- populations 48h after inhibitor treatment. RESULTS: Treatment of the DU145 prostate cancer cell line with the PLC gamma inhibitor resulted in cell cycle arrest with minimal increase in apoptosis. Sub-populations of prostate cancer cell lines have unique phenotypes (with CD44+ cells being more proliferative and CD54+ cells serving as better CD8+ T cell targets). We examined the effects of the PLC gamma inhibitor on these subpopulations and found that exposure decreased the percentage of both CD44+ (p=0.00007) and CD54+ (p=0.009) sub-populations. In contrast, treatment with Paclitaxel only effected CD44+ cells (p=0.0002). Combination treatment of the PLC gamma inhibitor and Paclitaxel however had synergistic effects on both CD44+ and CD54+ DU145 cells (p=0.005 and p=0.0002, respectively). CONCLUSIONS: These results suggest that a combination of PLC gamma inhibitor and Paclitaxel could be a novel strategy for the treatment of prostate cancer.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA