Abstract 5022: Atypical protein kinase C inhibitors abrogate malignant breast cancer

Abstract

Abstract Breast cancer is the most common cancer type with expected cases of approximately 284,200 according to the National Cancer Institute. Atypical Protein Kinase C (aPKC) plays a significant role in many cancer types. A positive correlation between elevated PKC levels and both the invasive and chemotactic potential of human breast cancer cell lines has been suggested in in-vitro studies. In addition, the atypical protein kinase C isoforms (aPKC), PKC- and PKC- are involved in the increased proliferation of several cancer types, including breast cancer and ovarian cancer. Hence, this project focused on utilizing aPKC inhibitors, ICA-1S (5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide and - Stat (8-hydroxy-1,3,6- naphthalenetrisulfonic acid), on two malignant breast cancer cell lines (T47D and BT549) to observe the effect on cell proliferation. To observe the effects of the aPKC inhibitors on the malignant breast cancer cells, cell proliferation assays were conducted, where cells were treated with ICA-1S, and - Stat for 72 hours (about 3 days). Furthermore, to observe if ICA-1S induces apoptosis in the malignant breast cancer cells, both the cell lines were treated with ICA-1S for 120 hours (about 5 days), and western blotting techniques were utilized. The results indicated that in T47D cell line, treatment with ICA-1S (50uM) and - Stat (10uM) caused 52% and 75% reduction in cell proliferation, respectively. Moreover, with BT549 cell line, treatment with - Stat (1uM) decreased the cell proliferation by 40%. Additionally, it was observed by western blotting that ICA-1S induces apoptosis in BT549 cell line. This was shown by an increase in the cleavage of caspase 3 and PARP, along with a decrease in survivin, and phospho-BAD. However, ICA-1S did not induce apoptosis in T47D cell line. Further investigation will be conducted on determining the effect of aPKC inhibitors on the proliferation, invasion, and migration of the malignant breast cancer cell lines. In addition, siRNA treatment will be applied to knockdown PKC- and PKC- and subsequent effect will be observed. In conclusion, PKC- and PKC- plays a significant role on breast cancer, and further investigation will be conducted to analyze these roles, which will lead to the determination of a signaling pathway via which atypical protein Kinase C functions in breast cancer. Citation Format: Nuzhat Nowshin Oishee, Khandker Mohammad Khalid, Dr. Mildred Acevedo-Duncan. Atypical protein kinase C inhibitors abrogate malignant breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5022.