Winni Nur Auli, Husniati Husniati, Nisa Yulianti Suprahman, Riri Fauziyya, Sarmoko Sarmoko, Arif Ashari, Ita Margaretha Nainggolan, Zetryana Puteri Tachrim, Puspa Dewi Narrij Lotulung, Rika Wulandari, Made Ninta Adyani, Bulan Rosita sari, Nurulita Nur Gustiantini, Gyska Amelia Fasya
Breast and prostate cancers are significant health concerns worldwide, demanding novel and effective therapeutic approaches. This study explores the potential of Gnetum gnemon seed metabolites as anticancers agent through metabolomic profiling and molecular docking analysis. Six metabolites from G. gnemon seed were identified, which met Lipinski's rule of five criteria, suggesting their drug-like properties. A panel of 10 molecular target proteins, including PTGS1, PTGS2, ESR1, SIRT1, SIRT3, SIRT5, AKT1, JAK2, BRAF, and NOS3, relevant to breast and prostate cancer pathways, were selected for molecular docking simulations. The binding interactions and free binding energy assessments identified gnetol and gnetin C as the most promising metabolites, showing strong interactions with multiple target proteins. Gnetol exhibited potential in targeting ESR1 and SIRT5, suggesting a mechanism for breast cancer inhibition. On the other hand, gnetin C emerged as a potent allosteric inhibitor of AKT1, potentially impacting breast and prostate cancer pathways. These findings highlight G. gnemon metabolites, particularly gnetol and gnetin C, as potential candidates for further preclinical and clinical studies as anti-breast and prostate cancer agents. © (2024), (Open Science Publishers LLP Inc.). All rights reserved.
Department of Pharmacy, Faculty of Sains, Institut Teknologi Sumatera, South Lampung, Indonesia; Research Center for Pharmaceutical Ingredient and Traditional Medicine, Research Organization for Health, National Research and Innovation Agency (BRIN), South Tangerang, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Bogor, Indonesia; School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia