ArticleScientific reports2016
Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
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- Insights into the Safety and Versatility of 4D Printed Intravesical Drug Delivery Systems.Pharmaceutics · 2023Article
- The widely reported but poorly studied ciliate family Folliculinidae (Protozoa, Ciliophora, Heterotrichea): a revision with notes on its taxonomy, morphology and phylogenetic relationships.Marine life science & technology · 2022Review
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- New contributions to the phylogeny of the ciliate class Heterotrichea (Protista, Ciliophora): analyses at family-genus level and new evolutionary hypotheses.Science China. Life sciences · 2021Article
- Preliminary Data Related to the Effect of Climacostol Produced by the Freshwater CiliateViruses · 2020Article
- Natural Function and Structural Modification of Climacostol, a Ciliate Secondary Metabolite.Microorganisms · 2020Review
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- XIAP as a Target of New Small Organic Natural Molecules Inducing Human Cancer Cell Death.Cancers · 2019Article
- Bioactivity and Structural Properties of Novel Synthetic Analogues of the Protozoan Toxin Climacostol.Toxins · 2019Article
- Autophagy controls neonatal myogenesis by regulating the GH-IGF1 system through a NFE2L2- and DDIT3-mediated mechanism.Autophagy · 2019Article
- The Natural Compound Climacostol as a Prodrug Strategy Based on pH Activation for Efficient Delivery of Cytotoxic Small Agents.Frontiers in chemistry · 2019Article
- Dysfunctional autophagy induced by the pro-apoptotic natural compound climacostol in tumour cells.Cell death & disease · 2018Article
- Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.Frontiers in immunology · 2018Article
- Deoxyarbutin displays antitumour activity against melanoma in vitro and in vivo through a p38-mediated mitochondria associated apoptotic pathway.Scientific reports · 2017Article
- Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.Oncology reports · 2017Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Climacostol, a compound produced by the ciliated protozoan Climacostomum virens, displayed cytotoxic properties in vitro. This study demonstrates that it has anti-tumour potential. Climacostol caused a reduction of viability/proliferation of B16-F10 mouse melanoma cells, a rapidly occurring DNA damage, and induced the intrinsic apoptotic pathway characterised by the dissipation of the mitochondrial membrane potential, the translocation of Bax to the mitochondria, the release of Cytochrome c from the mitochondria, and the activation of Caspase 9-dependent cleavage of Caspase 3. The apoptotic mechanism of climacostol was found to rely on the up-regulation of p53 and its targets Noxa and Puma. In vivo analysis of B16-F10 allografts revealed a persistent inhibition of tumour growth rate when melanomas were treated with intra-tumoural injections of climacostol. In addition, it significantly improved the survival of transplanted mice, decreased tumour weight, induced a remarkable reduction of viable cells inside the tumour, activated apoptosis and up-regulated the p53 signalling network. Importantly, climacostol toxicity was more selective against tumour than non-tumour cells. The anti-tumour properties of climacostol and the molecular events associated with its action indicate that it is a powerful agent that may be considered for the design of pro-apoptotic drugs for melanoma therapy.
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