The Role of Heat Shock Protein 90 in Cancer Cell Death Pathways: Implications for Natural Inhibitors in Therapeutic Strategies

Abstract

Heat shock proteins (HSPs) are crucial in regulating cell death pathways, particularly in cancer cells. These highly conserved proteins function as molecular chaperones, protecting critical client proteins from misfolding and degradation, thus maintaining intracellular integrity under stressed conditions. Interestingly, HSPs play a dual role in cancer: they help cancer cells survive stress and resist treatment, but they can also contribute to cell death under certain conditions. This contradictory behavior illustrates the complexity of HSP functions in cellular processes. HSPs especially, HSP90 a pivotal molecular chaperone that regulates cellular homeostasis and plays a critical role in cancer progression. Frequently overexpressed in various malignancies, HSP90 contributes to enhanced tumorigenicity, metastasis, and resistance to chemotherapy by stabilizing key client proteins involved in survival signaling pathways. HSP90 exhibits a dual role in cell death pathways, primarily inhibiting apoptosis and necrosis while also modulating autophagic processes.