Journal
JOURNAL OF ORAL PATHOLOGY & MEDICINE
Volume 48, Issue 1, Pages 17-23Publisher
WILEY
DOI: 10.1111/jop.12786
Keywords
ACTC1; EEF2; ionizing radiation; KRT6A; leptin; oral squamous cell carcinoma; reactive oxygen species
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico CNPq
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil
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Purpose Leptin, an important hormone controlling energy homeostasis, has been linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence indicates that head and neck cancer patients undergoing radiotherapy show decreased leptin levels after radiotherapy treatment. Thus, we investigated, through phenotypic and molecular analyses, whether leptin can compromise the therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells. Methods The human OSCC-derived cell lines SCC9 and SCC4 were treated with human recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro assays of cell migration, death, proliferation, and colony-forming ability. The reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry were also conducted. Results Leptin was able to increase cell proliferation, migration, and colony-forming ability, despite the suppressive effect induced by irradiation. Furthermore, the leptin promoted a significant reduction of ROS intracellular accumulation, and increased expression of the cancer-related proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells. Conclusions Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis.
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