Abstract Pancreatic cancer remains a formidable global health challenge. Current cancer treatments, such as chemotherapy are expensive and limited. Consequently, investigating alternative anticancer treatments, such as medicinal plants, is crucial. This study aimed to investigate the potential anticancer properties of a crude methanolic extract and isolated compounds from Carpobrotus edulis by targeting apoptotic machinery in pancreatic cancer cells (MIA PaCa2). Multiple assays, including Alamar blue, ATP, Hoechst staining, Caspase 3/7 activity, DNA fragmentation, and RT-qPCR, were conducted to assess apoptosis induction. The crude methanol and isolated compounds did not affect the MRC-5 non-cancerous cell line. Mechanistic investigations confirmed that the crude extract activated the extrinsic TNF-mediated apoptosis pathway, evidenced by a significant increase in TNF expression and caspase 3/7 activity, leading to DNA and nuclear fragmentation, chromatin condensation, and the formation of apoptotic bodies. The loss of cell confluence, supported by non-significant(p0,05) downregulation of STAT3, further suggested inhibited cell growth. While some changes were observed in the expression of p53, Bak1, and Fas for both the crude extract and isolated compounds, these were not statistically significant (p0,05). Protein-ligand docking studies of the identified 7,9-Ditert-butyl-oxaspiro 4.5 deca-6,9-diene-2,8-dione and 1-octadecanol proved the compounds as having high affinity for the selected ligands: TNFR, FADD, p53, Bak1, and STAT3. Future research will focus on the further purification and investigation of the most potent isolated compound. Citation Format: Lesetja Motadi, Ronald Makalapetlo, . Targeting apoptotic machinery using methanolic extracts of Carpobrotus edulis to suppress pancreatic cancer growth 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 3668.
Motadi et al. (Fri,) studied this question.