Abstract 7153: Selective atypical protein kinase C inhibitor reduces proliferation and promotes apoptosis in malignant endometrial cancer cells

Abstract Endometrial cancer is a type of uterine cancer. It starts in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most commonly diagnosed type of cancer that affects the gynecologic organs in the United States. Globally, endometrial cancer accounts for about 420,000 new cases and nearly 98,000 deaths annually (as of 2022), making it one of the most common gynecologic cancers worldwide. Endometrial cancer primarily affects postmenopausal women, with peak incidence between 60 and 70 years of age. Overall, it remains a disease largely associated with older, postmenopausal women. Among the Protein Kinase C (PKC) family, the atypical PKC (aPKC) subgroup, consisting of Protein Kinase C-iota (PKC-ι) and Protein Kinase C-zeta (PKC-ζ), has been implicated in cancer cell proliferation and survival. PKC-ι, in particular, is frequently overexpressed in various malignancies, including endometrial cancer. 5-amino-1-((1R, 2S, 3S, 4R)-2, 3-dihydroxy-4-methyl cyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S), an inhibitor selective for PKC-ι, has demonstrated anticancer activity in multiple tumor types such as glioblastoma, prostate, ovarian, and lung cancers. In our study, 50,000 Hec1A endometrial cancer cells were seeded in six-well plates and treated with various concentrations of ICA-1S. A concentration-dependent decrease in cell proliferation was observed, with reductions of 17%, 22%, 52%, 38%, and 58% at 1 µM, 5 µM, 10 µM, 20 µM, and 50 µM ICA-1S, respectively. The 10 µM concentration, which produced a significant inhibitory effect, was selected for subsequent experiments. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by Western Blot analysis showed a marked reduction in the expression and phosphorylation of PKC-ι. Similarly, there was a significant reduction in the levels of PKC-ζ and phosphorylated PKC-ζ. Additionally, expression of key apoptotic markers such as survivin, caspase-3, and poly (ADP-ribose) polymerase (PARP) was significantly decreased in ICA-1S-treated cells compared to untreated controls, suggesting induction of apoptosis. Future experiments will focus on identifying the signaling pathways affected by ICA-1S treatment through more Western Blotting, Immunofluorescence, Co-Immunoprecipitation, and Flow Cytometry to elucidate further the molecular mechanisms underlying the reduced proliferation and enhanced apoptosis observed in Hec1A cells following PKC-ι inhibition. Citation Format: Gaurab Raj Khanal, Shreejana Rimal, Grazielly Teodoro, Mildred Acevedo-Duncan. Selective atypical protein kinase C inhibitor reduces proliferation and promotes apoptosis in malignant endometrial cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7153.