Functional and Mechanistic Responses of the Adenocarcinoma Immortal Cell Line AGS to Treatment with the Nutraceutical Gallic Acid

Gastric cancer is a substantial global health burden that is associated with a 5-year survival rate at less than 30%. Current treatment options such as chemotherapy and surgery are associated with substantial deleterious side effects, necessitating the development of safe and effective means of treatment and prevention. The nutraceutical gallic acid (GA) is a secondary plant metabolite found naturally in plants. In cancer cells, GA has been shown to halt cancer cell growth, while leaving non-cancerous cells unaffected. To evaluate the effects of GA on cell cycle, we treated cells from the immortal gastric adenocarcinoma cancer line AGS, an epithelial cancer of the stomach lining with various doses of GA for a range of exposure times over 24 hours. We investigated both the functional response of AGS cells to gallic acid by measuring changes in cell cycle using flow cytometry and mechanistic responses of AGS to GA by evaluating changes in gene expression of treated compared to untreated AGS cells using quantitative PCR. We investigated eight genes associated with apoptosis (BAX2, BCL2 and RhoB) and cell cycle arrest pathways (MMP9, P21, CDK4, CDK6 and CYCLIN D1). We show that GA holds cell cycle in G_0/1 compared to untreated, and genes associated with cell cycle (CYCLIN D1), angiogenesis (MMP9), and apoptosis (BCL2) were up regulated. This work shows that GA does affect AGS cell proliferation by inducing apoptosis and arresting the cell cycle, and therefore may be an enticing therapeutic compound for gastric cancer that can be delivered via the consumption of natural products, such as fruit.