@misc{10481/90828,
year = {2023},
month = {11},
url = {https://hdl.handle.net/10481/90828},
abstract = {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.},
organization = {Grants from GOIB (AAEE0010/2017), Conselleria de Recerca
i Innovació},
publisher = {MDPI},
keywords = {Alkylphospholipids},
keywords = {Perifosine},
keywords = {Colorectal cancer},
title = {Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells},
doi = {10.3390/biology12121457},
author = {Torrens Mas, Margalida and Collado Solé, Alejandro and Sola Leyva, Alberto and Carrasco Jiménez, María Paz and Oliver, Jordi and Pons, Daniel Gabriel and Roca, Pilar and Sastre Serra, Jorge},
}