human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: Metformin is a well-established diabetes drug that prevents the onset of most types of human cancers in diabetic patients , especially by targeting cancer stem cells . Metformin exerts its protective effects by functioning as a weak " mitochondrial poison, " as it acts as a complex I inhibitor and prevents oxidative mitochondrial metabolism ( OXPHOS ) . Thus , mitochondrial metabolism must play an essential role in promoting tumor growth . To determine the functional role of " mitochondrial health " in breast cancer pathogenesis , here we used mitochondrial uncoupling proteins ( UCPs ) to genetically induce mitochondrial dysfunction in either human breast cancer cells ( MDA-MB-231 ) or cancer-associated fibroblasts ( hTERT-BJ1 cells ) . Our results directly show that all three UCP family members ( UCP-1/2/3 ) induce autophagy and mitochondrial dysfunction in human breast cancer cells , which results in significant reductions in tumor growth . Conversely , induction of mitochondrial dysfunction in cancer-associated fibroblasts has just the opposite effect . More specifically , overexpression of UCP-1 in stromal fibroblasts increases Î²-oxidation , ketone body production and the release of ATP-rich vesicles , which " fuels " tumor growth by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells . Hence , the effects of mitochondrial dysfunction are truly compartment-specific . Thus , we conclude that the beneficial anticancer effects of mitochondrial inhibitors ( such as metformin ) may be attributed to the induction of mitochondrial dysfunction in the epithelial cancer cell compartment . Our studies identify cancer cell mitochondria as a clear target for drug discovery and for novel therapeutic interventions .
    OUTPUT:

agent
resisting cell death
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
    ###
    INPUT: Metformin is a well-established diabetes drug that prevents the onset of most types of human cancers in diabetic patients , especially by targeting cancer stem cells . Metformin exerts its protective effects by functioning as a weak " mitochondrial poison, " as it acts as a complex I inhibitor and prevents oxidative mitochondrial metabolism ( OXPHOS ) . Thus , mitochondrial metabolism must play an essential role in promoting tumor growth . To determine the functional role of " mitochondrial health " in breast cancer pathogenesis , here we used mitochondrial uncoupling proteins ( UCPs ) to genetically induce mitochondrial dysfunction in either human breast cancer cells ( MDA-MB-231 ) or cancer-associated fibroblasts ( hTERT-BJ1 cells ) . Our results directly show that all three UCP family members ( UCP-1/2/3 ) induce autophagy and mitochondrial dysfunction in human breast cancer cells , which results in significant reductions in tumor growth . Conversely , induction of mitochondrial dysfunction in cancer-associated fibroblasts has just the opposite effect . More specifically , overexpression of UCP-1 in stromal fibroblasts increases Î²-oxidation , ketone body production and the release of ATP-rich vesicles , which " fuels " tumor growth by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells . Hence , the effects of mitochondrial dysfunction are truly compartment-specific . Thus , we conclude that the beneficial anticancer effects of mitochondrial inhibitors ( such as metformin ) may be attributed to the induction of mitochondrial dysfunction in the epithelial cancer cell compartment . Our studies identify cancer cell mitochondria as a clear target for drug discovery and for novel therapeutic interventions .
    OUTPUT:
