Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside
| العنوان: | Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside |
|---|---|
| المؤلفون: | Eliza Wyszko, Marta Orlicka-Płocka, Dorota Gurda-Wozna, Agnieszka Fedoruk-Wyszomirska |
| المصدر: | Apoptosis |
| بيانات النشر: | Springer US, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Cancer cells, Adenosine, Cellular respiration, Clinical Biochemistry, Pharmaceutical Science, Antineoplastic Agents, Apoptosis, Oxidative phosphorylation, Mitochondrion, Article, Oxidative Phosphorylation, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Neoplasms, Humans, Viability assay, Crabtree effect, Pharmacology, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, Cell growth, Biochemistry (medical), Galactose, Purine derivative, Cell Biology, Hep G2 Cells, Kinetin, Cell biology, Mitochondria, Culture Media, 030104 developmental biology, Metabolism, Glucose, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Kinetin riboside, Glycolysis |
| الوصف: | Small-molecule compound-based therapies have provided new insights into cancer treatment against mitochondrial impairment. N6-furfuryladenosine (kinetin riboside, KR) is a purine derivative and an anticancer agent that selectively affects the molecular pathways crucial for cell growth and apoptosis by interfering with mitochondrial functions and thus might be a potential mitotoxicant. Metabolism of cancer cells is predominantly based on the Crabtree effect that relies on glucose-induced inhibition of cell respiration and thus on oxidative phosphorylation (OXPHOS), which supports the survival of cancer cells in metabolic stress conditions. The simplest way to circumvent this phenomenon is to replace glucose with galactose in the culture environment. Consequently, cells become more sensitive to mitochondrial perturbations caused by mitotoxicants. In the present study, we evaluated several cellular parameters and investigated the effect of KR on mitochondrial functions in HepG2 cells forced to rely mainly on OXPHOS. We showed that KR in the galactose environment is a more potent apoptosis-inducing agent. KR decreases the mitochondrial membrane potential, reduces glutathione level, depletes cellular ATP, and induces reactive oxygen species (ROS) production in the OXPHOS state, leading to the loss of cell viability. Taken together, these results demonstrate that KR directly acts on the mitochondria to limit their function and that the sensitivity of cells is dependent on their ability to cope with energetic stress. |
| اللغة: | English |
| تدمد: | 1573-675X 1360-8185 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::906a8267476ed44da592ffb3caf9de47 http://europepmc.org/articles/PMC7679298 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....906a8267476ed44da592ffb3caf9de47 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1573675X 13608185 |
|---|