Abstract 5430: Hematopoietic stem cells conditioned media alters the colorectal cancer cells metabolism by disrupting the mitochondrial bioenergetics in vitro

Abstract Colorectal cancer (CRC) is a major public health issue, and mitochondrial dysfunction plays a pivotal role in its development. Mitochondria, the "powerhouses of the cell, " are particularly important in cancer cells due to their high energy demands. The dynamic nature of mitochondria, including their ability to fuse and divide, is crucial for their role in signal transduction and metabolism. Enhanced mitochondrial fission, a process that divides mitochondria into smaller fragments, promotes the metabolic reprogramming of CRC cells. These reprogramming fuels cell proliferation, metastasis, and resistance to chemotherapy. However, excessive fission can also trigger apoptosis, leading to cell death. Our work shows that hematopoietic stem cells (HSCs) derived conditioned media (CM) altered metabolic activities by altering the mitochondrial oxidative phosphorylation through an excessive mitochondrial fission by upregulating the Drp-1 and downregulating the fusion protein Opa-1 and Mito-fusion proteins. Moreover, HSCs-CM dysregulated the electron transport chain complexes with high dysregulation of complex-III. Our integrated omics and mitochondria-targeted studies provided the dysregulation of the critical proteins involved in mitochondrial bioenergetics in CM treated CRCs. Our findings reveal the therapeutic nature of HSCs-conditioned media for colorectal cancer therapy. Citation Format: Sumit Mallick, Sudheer P. Shenoy, Bipasha Bose. Hematopoietic stem cells conditioned media alters the colorectal cancer cells metabolism by disrupting the mitochondrial bioenergetics in vitro [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 5430.