ReferenceID 2600
Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis
J Clin Invest
Mitochondrial electron transport chain complex I (ETCC1) is the essential core of cancer metabolism, yet potent ETCC1 inhibitors capable of safely suppressing tumor growth and metastasis in vivo are limited. From a plant
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Record Fields
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- Reference Id
- 2600
- Evidence Id
- 19190
- Core Evidence Id
- 19190
- Source Reference Id
- 5198
- Herb2 Reference Id
- HBREF005995
- Subject Paper Key
- HBIN039348_34623325
- Pubmed Id
- 34623325
- Doi
- 10.1172/JCI139933
- Paper Title
- Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis
- Paper Abstract
- Mitochondrial electron transport chain complex I (ETCC1) is the essential core of cancer metabolism, yet potent ETCC1 inhibitors capable of safely suppressing tumor growth and metastasis in vivo are limited. From a plant extract screening, we identified petasin (PT) as a highly potent ETCC1 inhibitor with a chemical structure distinct from conventional inhibitors. PT had at least 1700 times higher activity than that of metformin or phenformin and induced cytotoxicity against a broad spectrum of tumor types. PT administration also induced prominent growth inhibition in multiple syngeneic and xenograft mouse models in vivo. Despite its higher potency, it showed no apparent toxicity toward nontumor cells and normal organs. Also, treatment with PT attenuated cellular motility and focal adhesion in vitro as well as lung metastasis in vivo. Metabolome and proteome analyses revealed that PT severely depleted the level of aspartate, disrupted tumor-associated metabolism of nucleotide synthesis and glycosylation, and downregulated major oncoproteins associated with proliferation and metastasis. These findings indicate the promising potential of PT as a potent ETCC1 inhibitor to target the metabolic vulnerability of tumor cells.
- Journal
- J Clin Invest
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Cancer
- Paper Title Cn
- Paper Title En
- Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis
- Bilingual Status
- semi_complete