Abstract 4134: An inhibitor of the atypical protein kinase C-ζ impede the growth of gastric cancer cells by inducing apoptosis

The global statistics on gastric cancer suggest that it is the fifth most common type of cancer in terms of prevalence and third-most common type in terms of death rate. The considerably high mortality of gastric cancer is mainly because of the fact that it is mostly diagnosed when the disease has progressed to the advanced stage. While the bacterium Helicobacter pylori is known to be the most common cause of gastric cancer, other notable risk factors also include high salt intake, age and diets lacking in fruits and vegetables. Demographic data have revealed that the regions of East Asia, Eastern Europe and South America are notable hotspots of this type of cancer. Endoscopic resection is considered as the major treatment procedure for early detected gastric cancer while those diagnosed in later stages are treated with surgeries such as D2 lymphadenectomy. Previously, the Atypical Protein Kinases C (aPKCs) - ζ and ι - have been documented to play significant roles in elevated cell proliferation in various cancer types. Here, an inhibitor of the aPKC-ζ, known as ζ-stat (8-hydroxy-1,3,6- naphthalenetrisulfonic acid), that specifically inhibits the aPKC-ζ on a gastric cancer cell line (i.e., AGS) was used to observe its effects on cell proliferation. In separate trials, AGS cells were treated with ζ-stat for 72 hours (about 3 days). An assortment of drug concentrations for the inhibitor was tried and the analysis of the cell count demonstrated that the cell proliferation decreases were statistically significant for the drug in all concentrations. The highest decrease was observed at 10 µM (P < 0.0001) as the number of cells diminished to approximately 44%. Our previous research has revealed that ζ-stat downregulates the aPKC-ζ by interfering with established cancer pathways to cause cell deaths. Henceforth, Western Blot analysis of AGS cells treated with ζ-stat have shown evidence of apoptosis. There have been considerable decreases in the levels of total PARP, Caspase 3 and Survivin. Likewise, levels of cleaved-Caspase 3 and cleaved-PARP have also increased along with the mitochondrial apoptotic marker Cytochrome C. Current investigations include how ζ-stat play into some of the well-established gastric cancer pathways to lead to cell deaths with techniques such as Western Blot analysis, Immunoprecipitation Assays and Flow cytometry. Citation Format: Abiral Hasib Shourav, Abigail Olatunji, Mahfuza Marzan, Radwan Ebna Noor, Mildred Acevedo-Duncan. An inhibitor of the atypical protein kinase C-ζ impede the growth of gastric cancer cells by inducing apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4134.