| Grant number: | 20/06613-8 |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| Start date: | November 01, 2020 |
| End date: | October 31, 2024 |
| Field of knowledge: | Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology |
| Principal Investigator: | Leticia Veras Costa Lotufo |
| Grantee: | Amanda Soares Hirata |
| Host Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM |
| Associated scholarship(s): | 22/05133-8 - Role of collagen receptors DDR in mechanosignaling and therapeutic resistance in melanoma, BE.EP.DD |
Abstract The most aggressive Skin Cancers is Melanoma, which has a high mortality rate and increasing incidence. The BRAFV600E protein ihibitors, the most recurrent mutation in Melanoma, came at the beginning of the decade as promising treatments, however, the high cost, adverse effects and frequent tumor resistance are limiting its therapeutic success. Given this, there is an urgent need to discover new drugs for this type of Cancer. Seriniquinone (SQ) was isolated from the marine bacterium Serinicoccus sp. and it showed selective cytotoxicity for melanoma cells at nM concentrations. The same study also found that SQ binds to dermicidin protein (DCD), modulating its expression, generating death by autophagy followed by apoptosis. Our preliminary results showed that vemurafenib (PLX4032) resistant melanoma cells remain sensitive to SQ treatments. This way, SQ becomes a promising alternative in the treatment of resistant cells. The present project aims to characterize the antitumor activity of SQ in PLX4032 resistant cells, comparing it with its synthetic derivative LT406, and the effects on cell death pathways and on the DCD expression. For better understanding of mechanism of action, the analysis of the transcriptome and proteome of the treated cells and controls will be carried out, seeking to understand the role of dermicidin in SQ and LT406 activity and in resistance to PLX4032. In addition, the study of compounds in 3D models of cellular spheroids and reconstructed skin in vitro is planned as a strategy to evaluate their actions in models that best represent the complexity of the tumor environment. (AU) | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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