Abstract 3470: Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD

Abstract

Abstract Aggressive and metastatic prostate cancers are highly lethal tumors and are one of the leading causes of death among men. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant cancer cells. There is a gap in knowledge relating to which intracellular chemicals confer the emergence of therapy-resistant prostate cancer cells, which intracellular chemicals are responsible for prostate cancer survival and which chemicals regulate intracellular signaling pathways in prostate cancer. To address this critical problem, we investigated two drugs that act as inhibitors of atypical protein kinase C. The objective of this study was to test the effectiveness of ACPD [Diabetes. 63:2690-2701 (2014)] as an atypical PKC inhibitor and ICA-1 as an inhibitor of PKC-iota [The Inter. J. Biochem. & Cell Biol. 43:784-794(2011)]. DU-145 prostate carcinoma cells and non-malignant prostate RWPE-1 cells were each cultivated in separate flasks. They were treated with drugs of interest for three consecutive days. The cells were counted before and after the treatments and a statistical analysis was performed. The cells were lysed and levels of PKC-iota and PKC-zeta were measured by Western blotting and immunoprecipitation. Our preliminary results demonstrated that treatment of DU-145 showed a statistically significant decrease in cells that was proportional to the concentration in both drugs. Treatment of the RWPE-1 cells showed no statistically significant change in population. Western blotting showed that both drugs decreased PKC-iota. In conclusion ACPD is an effective inhibitor of PKC-iota and PKC-zeta and consequently significantly reduced the neogenesis of the prostate DU-145 carcinoma cells while having negligible effect on the non-malignant prostate RWPE-1 cells. Citation Format: Andre H. Apostolatos, Christopher Apostolatos, Mildred Acevedo-Duncan. Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3470. doi:10.1158/1538-7445.AM2015-3470