Inhibitory Apoptosis Proteins (IAPs) as therapeutic targets in melanoma: studies with prodiginines in vemurafenibe-resistant cells

• Grant number: 17/09022-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2017
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Leticia Veras Costa Lotufo
• Grantee: Paola Cristina Branco
• 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

Abstract

Apoptosis inhibitory proteins (IAPs) are a family of proteins that share the BIR-like domain that recognizes caspases, and their interaction with them is able to inhibit the apoptotic cascade. Among the members of this family, we highlight the survin whose expression is minimal or even absent in normal cells, however it is overexpressed in tumor cells, what constitutes it as a possible therapeutic target. It has been previously reported that members of this family are overexpressed in melanoma. Melanoma is the most aggressive form of skin cancer presenting high mortality rates. Currently much of the treatment is based on vemurafenib, a B-Raf inhibitor that selectively recognizes the mutation in this protein. Although there is a considerable success rate in this therapy, approximately 20% of patients present relapse and an intrinsic resistance to therapy. Therefore, new therapeutic alternatives are necessary. It is noteworthy that survivin has been related to resistance in melanoma cells. Prodigyins, a group of secondary metabolites extracted from bacteria that have cytotoxic and immunomodulatory activity, have their activity related to the modulation of survivin. Our preliminary trials demonstrated that prodigiosin and derivatives have cytotoxicity in the order of nanomolar including vemurafenib resistant cells, configuring a therapeutic possibility for melanoma. Given the above, it is necessary to evaluate the effects of prodigiosin and derivatives in parenteral and resistant melanoma strains of vemurafenib, its mechanism of action and to evaluate the role of survivin in this therapy.

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRANCO, PAOLA C.; PONTES, CRISTINE A.; REZENDE-TEIXEIRA, PAULA; AMENGUAL-RIGO, PEP; ALVES-FERNANDES, DEBORA K.; MARIA-ENGLER, SILVYA STUCHI; DA SILVA, ALISON B.; PESSOA, OTILIA DEUSDENIA L.; JIMENEZ, PAULA C.; MOLLASALEHI, NILOUFAR; et al. Survivin modulation in the antimelanoma activity of prodiginines. European Journal of Pharmacology, v. 888, DEC 5 2020. (15/17177-6, 17/09022-8, 17/11285-7)

SAHM, BIANCA DEL B.; PERES, JADE; REZENDE-TEIXEIRA, PAULA; SANTOS, EVELYNE A.; BRANCO, PAOLA C.; BAUERMEISTER, ANELIZE; KIMANI, SERAH; MOREIRA, EDUARDA A.; BISI-ALVES, RENATA; BELLIS, CLAIRE; et al. Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins. RONTIERS IN CHEMISTR, v. 8, p. 9-pg., 2020-03-03. (17/09022-8, 18/24865-4, 18/08400-1, 15/17177-6, 19/02008-5)

JIMENEZ, PAULA C.; WILKE, DIEGO V.; BRANCO, PAOLA C.; BAUERMEISTER, ANELIZE; REZENDE-TEIXEIRA, PAULA; GAUDENCIO, SUSANA P.; COSTA-LOTUFO, LETICIA V.. Enriching cancer pharmacology with drugs of marine origin. British Journal of Pharmacology, v. 177, n. 1, p. 3-27, JAN 2020. (17/17648-4, 17/09022-8, 15/17177-6)

SAHM, BIANCA DEL B.; PERES, JADE; REZENDE-TEIXEIRA, PAULA; SANTOS, EVELYNE A.; BRANCO, PAOLA C.; BAUERMEISTER, ANELIZE; KIMANI, SERAH; MOREIRA, EDUARDA A.; BISI-ALVES, RENATA; BELLIS, CLAIRE; et al. Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins. FRONTIERS IN CHEMISTRY, v. 8, MAR 3 2020. (18/24865-4, 15/17177-6, 19/02008-5, 18/08400-1, 17/09022-8)

MATEUS REIS-SILVA, CATARINA SOFIA; BRANCO, PAOLA CRISTINA; LIMA, KELI; SILVA, FABIANA LIMA; HRIHOROWITSCH MORENO, PAULO ROBERTO; GUALLAR, VICTOR; COSTA-LOTUFO, LETICIA VERAS; MACHADO-NETO, JOAO AGOSTINHO. Embelin potentiates venetoclax-induced apoptosis in acute myeloid leukemia cells. TOXICOLOGY IN VITRO, v. 76, OCT 2021. (17/09022-8, 19/23864-7, 15/17177-6, 18/06522-2)

WILKE, V, DIEGO; JIMENEZ, PAULA C.; BRANCO, PAOLA C.; REZENDE-TEIXEIRA, PAULA; TRINDADE-SILVA, AMARO E.; BAUERMEISTER, ANELIZE; LOPES, NORBERTO PEPORINE; COSTA-LOTUFO, V, LETICIA. Anticancer Potential of Compounds from the Brazilian Blue Amazon. Planta Medica, v. 87, n. 01/02, NOV 2020. (15/17177-6, 14/50926-0, 17/09022-8, 17/17648-4)

REZENDE-TEIXEIRA, PAULA; DUSI, RENATA G.; JIMENEZ, PAULA C.; ESPINDOLA, LAILA S.; COSTA-LOTUFO, V, LETICIA. hat can we learn from commercial insecticides? Efficacy, toxicity, environmental impacts, and future development. Environmental Pollution, v. 300, MAY 1 2022. (17/09022-8, 14/50926-0, 15/17177-6, 17/17648-4)