title: Cancer Stem Cells in Small Cell Lung Cancer Cell Line H446: Higher Dependency on Oxidative Phosphorylation and Mitochondrial Substrate-Level Phosphorylation than Non-Stem Cancer Cells.
abstract: Recently, targeting cancer stem cells (CSCs) metabolism is becoming a promising therapeutic approach to improve cancer treatment outcomes. However, knowledge of the metabolic state of CSCs in small cell lung cancer is still lacking. In this study, we found that CSCs had significantly lower oxygen consumption rate and extracellular acidification rate than non-stem cancer cells. Meanwhile, this subpopulation of cells consumed less glucose, produced less lactate and maintained lower ATP levels. We also revealed that CSCs could produce more ATP through mitochondrial substrate-level phosphorylation during respiratory inhibition compared with non-stem cancer cells. Furthermore, they were more sensitive to suppression of oxidative phosphorylation. Therefore, oligomycin (inhibitor of oxidative phosphorylation) could severely impair sphere-forming and tumor-initiating abilities of CSCs. Our work suggests that CSCs represent metabolically inactive tumor subpopulations which sustain in a state showing low metabolic activity. However, mitochondrial substrate-level phosphorylation of CSCs may be more active than that of non-stem cancer cells. Moreover, CSCs showed preferential use of oxidative phosphorylation over glycolysis to meet their energy demand. These results extend our understanding of CSCs metabolism, potentially providing novel treatment strategies targeting metabolic pathways in small cell lung cancer.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.|Department of blood transfusion, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Jin
authors.affiliation: Research Center for Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D009840:Oligomycins; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose