2026-05-22T23:02:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/237182024-11-28T21:34:29Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Torrens-Mas, Margalida author Collado-Solé, Alejandro author Sola-Leyva, Alberto author Carrasco-Jiménez, María Paz author Oliver, Jordi author Pons, Daniel-Gabriel author Roca, Pilar author Sastre-Serra, Jorge author 2023-11-22 Alkylphospholipids (APLs) have been studied as anticancer drugs that interfere with biological membranes without targeting DNA. Although their mechanism of action is not fully elucidated yet, it is known that they disrupt the intracellular trafficking of cholesterol and its metabolism. Here, we analyzed whether APLs could also interfere with mitochondrial function. For this purpose, we used HT29 colorectal cancer cells, derived from a primary tumor, and SW620 colorectal cancer cells, derived from a metastasis site. After treatment with the APLs miltefosine and perifosine, we analyzed various mitochondrial parameters, including mitochondrial mass, cardiolipin content, mitochondrial membrane potential, H2O2 production, the levels of oxidative phosphorylation (OXPHOS) complexes, metabolic enzymes activity, the oxygen consumption rate, and the levels of apoptosis and autophagy markers. APLs, especially perifosine, increased mitochondrial mass while OXPHOS complexes levels were decreased without affecting the total oxygen consumption rate. Additionally, we observed an increase in pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) levels and a decrease in lactate dehydrogenase (LDH) activity, suggesting a metabolic rewiring induced by perifosine. These alterations led to higher mitochondrial membrane potential, which was potentiated by decreased uncoupling protein 2 (UCP2) levels and increased reactive oxygen species (ROS) production. Consequently, perifosine induced an imbalance in mitochondrial function, resulting in higher ROS production that ultimately impacted cellular viability. Torrens-Mas M, Collado-Solé A, Sola-Leyva A, Carrasco-Jiménez MP, Oliver J, Pons DG, et al. Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells. Biology (Basel). 2023 Nov 22;12(12):1457. 10.3390/biology12121457 2079-7737 Biology https://hdl.handle.net/20.500.13003/20220 38132283 https://hdl.handle.net/20.500.12105/23718 Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells