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

Muzinic, N. Rezic; Mastelic, A.; Markotic, A.; Culic, V. Cikes; Ross, A.; Vuica-Ross, M.; Barker, D.; Reynisson, J.

Abstract

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 dis-covered 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 48 h 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 48 h after inhibitor treatment.

Results: Treatment of the DU145 prostate cancer cell line with the PLC gamma inhibitor resulted in cell cycle arrest with mini-mal 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.

Citation

Muzinic, N. R., Mastelic, A., Markotic, A., Culic, V. C., Ross, A., Vuica-Ross, M., …Reynisson, J. (2014, August). The effect of a phospholipase C gamma inhibitor on the proliferation and phenotype of Du145 prostate cancer cells. Poster presented at FEBS EMBO 2014 Conference, Paris, France

• Presentation Conference Type: Poster
• Conference Name: FEBS EMBO 2014 Conference
• Conference Location: Paris, France
• Start Date: Aug 30, 2014
• End Date: Sep 4, 2014
• Deposit Date: Jun 13, 2023
• Keywords: prostate cancer; phospholipase C inhibitor
• Publisher URL: https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.12919
• Additional Information: PDF link published 27 August 2014;; https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.12919