Abstract 6780: Discovering novel inhibitors of the chaperone Hsp90 for cancer treatment: A plant-based approach

Abstract We investigated the effect of small molecules extracted from the latex of Calotropis procera (CPPE) to act as inhibitors of Heat Shock Protein 90 (HSP90), a key molecular chaperone co-opted by cancer cells for survival and proliferation. Current HSP90 inhibitors often activate the heat shock response, reducing their long-term efficacy. While CPPE has been shown to have toxic effects on cancer cells, its exact mechanism of action, including its potential to inhibit HSP90, has yet to be evaluated. Using flow cytometry, gene expression and protein quantification analysis, and mass spectroscopy techniques, we evaluated the effects of CCPE small molecules on triple-negative breast cancer cells (TNBCs) compared to 17-AAG, a known HSP90 inhibitor. We observed a dose-dependent increase in cell death with graded doses of CPPE compared to 17-AAG. Additionally, our findings from the MTT assay and flow cytometry demonstrated that treatment with CPPE led to a decrease in cell viability and the initiation of cell death pathways such as apoptosis and necrosis. Notably, western blot analysis suggests the absence of heat shock responses in cells treated with CPPE compared to 17-AAG. These findings support our hypothesis, indicating that small molecules present in CPPE show promise as candidates for HSP90 inhibitors. Further investigations to gain deeper insights into CPPE mechanisms as well as characterizing its bioactive compounds are ongoing. This research highlights the importance of natural product-based drug discovery in cancer treatment Citation Format: Chidera P. Ogbu, Taoufik Llbiyi, Vamsi Krishna Kommalapati, Ahmed Chadli. Discovering novel inhibitors of the chaperone Hsp90 for cancer treatment: A plant-based approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6780.