Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 04 30 1 11 Neda Ahmad Nejad Ahranjani Department of Biology, Faculty of Basic Sciences, Nabi Akram University, Tabriz, Iran Maryam Farghadan Human and Animal Cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran Mehrnoosh Pashaei Department of Research Development and Coordination, Deputy for Research and Technology, Ministry of Health and Medical Education, Tehran, Iran Sepideh Ashouri Movassagh Human and Animal Cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran Seyed Abolhassan Shahzadeh Fazeli Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 2025 12 04 2026 01 31 Gastric cancer is among the most prevalent malignancies worldwide, with a poor prognosis in advanced stages. Overexpression of human epidermal growth factor receptor 2 (HER2, also known as ERBB2) and heat shock protein 90 alpha (HSP90AA1, also known as HSP90α) has been associated with tumor progression. Anethum graveolens, a medicinal plant from the Apiaceae family, has demonstrated anticancer properties in previous studies. This study aimed to evaluate the effects of A graveolens methanolic extract on apoptosis and the expression of HER2, HSP90α, tumor protein p53 (TP53), and caspase-3 genes in the human gastric adenocarcinoma cell line (AGS). A methanolic extract of the aerial parts of A graveolens was prepared. Cytotoxicity was assessed in AGS and human gingival fibroblast (HUGU) cell lines using the -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Gene expression was measured by real-time PCR, and apoptosis was evaluated using Annexin V/propidium iodide (PI) staining followed by flow cytometry. The methanolic extract exhibited dose-dependent cytotoxicity, with a half-maximal inhibitory concentration (IC50) of 1280 μg/mL in AGS cells. Gene expression analysis revealed significant downregulation of HER2 and upregulation of HSP90α, TP53, and caspase-3 in treated AGS cells compared to controls. Apoptosis rates were significantly higher in treated AGS cells, confirming the proapoptotic effect of the extract. A graveolens exerts cytotoxic and proapoptotic effects in AGS cells and modulates key genes involved in gastric cancer progression. These findings suggest its potential as a natural therapeutic candidate for gastric cancer, warranting further preclinical and clinical investigations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4687 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4687/2333