ArticleOncotarget2016
Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Update on the intriguing roles of AQP4 expression and redistribution in the progression and treatment of glioma.Annals of medicine · 2024Review
- Ring finger protein 180 suppresses cell proliferation and energy metabolism of non-small cell lung cancer through downregulating C-myc.World journal of surgical oncology · 2022Article
- Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines.Frontiers in oncology · 2021Article
- Gamabufotalin Inhibits Osteoclastgenesis and Counteracts Estrogen-Deficient Bone Loss in Mice by Suppressing RANKL-Induced NF-κB and ERK/MAPK Pathways.Frontiers in pharmacology · 2021Article
- The NEDD4-1 E3 ubiquitin ligase: A potential molecular target for bortezomib sensitivity in multiple myeloma.International journal of cancer · 2020Article
- Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794.Cell proliferation · 2020Article
- WWP2 Is One Promising Novel Oncogene.Pathology oncology research : POR · 2019Review
- Dysregulated expressions of PTEN, NF-κB, WWP2, p53 and c-Myc in different subtypes of B cell lymphoma and reactive follicular hyperplasia.American journal of translational research · 2019Article
- Disruption of OCT4 Ubiquitination Increases OCT4 Protein Stability and ASH2L-B-Mediated H3K4 Methylation Promoting Pluripotency Acquisition.Stem cell reports · 2018Article
- Review
- EBP50 suppresses the proliferation of MCF-7 human breast cancer cells via promoting Beclin-1/p62-mediated lysosomal degradation of c-Myc.Acta pharmacologica Sinica · 2018Article
- Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM.
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