Effects of hypoxia induced alterations on mitochondrial dynamics in malignant melanoma cancer stem cells

Project no. 30755 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

<p>Malignant melanoma is an aggressive skin cancer with high mortality and morbidity rates. Cancer stem cells are at the center of the mechanisms of tumor formation, progression and resistance to treatment. Malignant melanoma stem cells, identified by the CD133+ marker, are characterized by hypoxia-adapted energy metabolism and differences in mitochondrial function. Hypoxia-inducing factor 1-alpha (Hif1a) plays a key role in the survival and resistance mechanisms of these cells. Mitochondria are central to cellular energy production, oxidative stress regulation and apoptosis processes, making them an important organelle for therapeutic targeting of cancer stem cells. The main aim of this study was to investigate the effects of Hif1a silencing on hypoxia and oxidative stress mechanisms by examining the mitochondria-based biochemical and biophysical properties of malignant melanoma cancer stem cells. In the study, malignant melanoma stem cells (CD133+) were isolated by flow cytometry and compared with CD133- cells. Hif1a gene expression was silenced using siRNA and then cell lines were analyzed by ATR-FTIR spectroscopy, mitochondria imaging, ROS analysis and apoptosis detection. Results showed that CD133+ cells exhibited higher hypoxic character and mitochondrial biochemical differences than CD133- cells. Hif1a silencing decreased the hypoxic response, decreased ROS levels and increased apoptosis rates. ATR-FTIR analysis revealed significant changes in the mitochondrial lipid and protein structures of CD133+ cells. This study provides important data on hypoxia and mitochondria-driven processes in malignant melanoma cancer stem cells. It has been shown that Hif1a silencing could be a potential strategy to target the survival mechanisms of cancer stem cells. The study makes a unique contribution to the literature in terms of both cancer biology and therapeutic approaches.</p>

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