Journal
CANCER GENOMICS & PROTEOMICS
Volume 17, Issue 6, Pages 781-793Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/cgp.20232
Keywords
Gigantol; Dendrobium draconis; MYC; proteomics; cell proliferation; lung cancer
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Funding
- 90th Anniversary of Chulalongkorn University, Rachadapisek Sompote Fund
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Background: Gigantol is a pharmacologically active bibenzyl compound exerting potential anticancer activities. At non-toxic concentrations, it reduces cancer stem cell properties and tumorigenicity. The mechanisms of the effects of gigantol on cancer cell growth are largely unknown. This study aimed to unravel the molecular profile and identify the prominent molecular mechanism of the effects of gigantol in controlling lung cancer cell proliferation. Materials and Methods: Proteomics and bioinformatics analysis were used accompanied by experimental molecular pharmacology approaches. Results: Gigantol exhibited antiproliferative effects on human lung cancer cells confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide proliferation assay and colony growth assay. The protein profile in response to gigantol treatment associated with regulation of cell proliferation was analyzed to determine the prominent protein targets. Among the significant hub proteins, MYC, an important proto-oncogene and proliferation-promoting transcription factor, was down-regulated with the highest number of protein-protein interactions. MYC downregulation was confirmed by western blot analysis. The upstream regulator of MYC, Glycogen synthase kinase 3 beta (GSK3 beta) was found to be responsible for MYC destabilization mediated by gigantol. Gigantol facilitated GSK3 beta function and resulted in the increase of MYC-ubiquitin complex as evaluated by immunoprecipitation. Conclusion: Gigantol was found to inhibit lung cancer proliferation through induction of GSK3 beta-mediated MYC ubiquitin-proteasome degradation. These data suggest gigantol to be a promising candidate for novel strategy in inhibition of lung cancer.
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