ASHS 2024 Conference

Annonacin is a natural compound found in the fruit of a number of members of the Annonaceae family, including soursop and Asimina triloba. This compound has promise in targeting vital metabolic pathways, inhibiting mitochondrial complex I, and exploiting the altered energy dynamics of cancer cells that lead to apoptosis. Non-small cell Lung Cancer (NSCLC) accounts for approximately 80% of all lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Despite advancements in cancer treatment, the five-year survival rate of NSCLC is low, justifying the urgent need for innovative and effective therapeutic approaches. The aberrant energy metabolism, which is a hallmark of cancer, including NSCLC, known as the Warburg effect, makes it a potential target for therapeutic interventions. In addition, 2-Deoxy-D-glucose (2DG) is a glucose analog widely studied for its ability to target the glycolytic pathway of energy metabolism of cancer. The potential combination of Annonacin and 2DG acting synergistically to inhibit the growth of A549 NSCLC cells could lead to new treatment options. The objective of this study was to examine glycolytic and mitochondrial complex I inhibitors individually and in combination to target energy metabolism to inhibit A549 NSCLC cell growth as novel antitumor agents. The study was carried out in an in vitro model system using the A549 NSCLC cell line, where the NL20 Bronchial Epithelium cell line was used as a parallel control. Cells were treated with 0 µM, 2 µM, 4 µM, and 6 µM concentrations of Annonacin and 0 mM, 2.5 mM, 5 mM, and 10 mM concentrations of 2DG, both individually and in combination in triplicate experimental design with control. The MTT assay was employed to determine immediate cell viability and assess the applied treatment's cytotoxic effects. The oxidative stress in treated and control cells was determined through superoxide dismutase and glutathione peroxidase assays. Furthermore, the long-term proliferative capacity of the cells post-treatment was examined using a colony-forming assay. The implications of the combined application of 2DG and Annonacin on A549 NSCLC cell viability and potential as a treatment of NSCLC will be discussed. These findings need further investigation to elucidate the underlying mechanisms and explore the in vivo and clinical applicability details for the combined administration of Annonacin and 2DG's use in NSCLC treatment.