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| Author(s): |
Daisy Machado
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2012-02-07 |
| Examining board members: |
Carmen Veríssima Ferreira;
Silvya Stuchi Maria Engler;
Mauricio da Silva Baptista;
Carmen Silvia Passos Lima;
Alessandro dos Santos Farias
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| Advisor: | Silvia Mika Shishido; Carmen Veríssima Ferreira |
| Abstract | |
Melanoma is the most aggressive type of skin disorder and a major cause of death by skin's disease due to its highly metastatic ability. In terms of melanoma therapeutic strategies has given emphasis on control of resistance and metastasis. Our group observed that irradiated riboflavin (RF) induces apoptosis of prostate cancer cells, kidney cancer cells and myeloid leukemia. Therefore, the goal of this study was to employ irradiated RF for modulating chemical and genetically signal pathways associated with melanoma survival, resistance and aggressiveness. Thus, in this manuscript data about the influence of RF in different cellular metabolic aspects of murine melanoma (B16F10) such as cytotoxicity, adhesion, invasion, migration, colony formation and signal transduction mediators Src kinase, mTOR and sonic hedgehog components, will be presented. In all experiments the RF was previously irradiated with UVA (dose of 9 J/cm²). Inhibition of cell proliferation was observed with IC50 value of 50 ?M. Interestingly, RF in a nanomolar concentration inhibited the formation of colonies. In addition, 1 ?M irradiated RF caused a reduction of B16F10 cells adhesion. The ability of migration and invasion of melanoma cells was reduced in the presence of RF, however, those cells response was dose-independent. The activity and expression of metalloproteinases were diminished indicating reduction of cellular invasiveness capacity. Sonic hedgehog and PI3K/mTOR pathways were negatively modulated and the expression of p53 and PTEN were increased in melanoma cells treated with irradiated RF. The findings showed in this study brought out flavins as promising candidates for pharmacological intervention of melanoma (AU) | |
| FAPESP's process: | 09/00144-7 - Chemical and genic modulation of signaling pathways as strategy to control the aggressiveness of the melanoma |
| Grantee: | Daisy Machado |
| Support Opportunities: | Scholarships in Brazil - Doctorate |