In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine

Autor(es)

Porta, Lucas C. ^[1] ; Campeiro, Joana D. ^[1] ; Papa, Giovanna B. ^[1] ; Oliveira, Eduardo B. ^[2] ; Godinho, Rosely O. ^[1] ; Rodrigues, Tiago ^[3] ; Hayashi, Mirian A. F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med EPM, Dept Farmacol, Rua 3 Maio 100, Ed INFAR, 3rd Floor, BR-04044020 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo USP RP, Dept Bioquim & Imunol, Ribeirao Preto - Brazil

^[3] Univ Fed ABC, Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 185, p. 64-71, OCT 15 2020.
• Citações Web of Science: 0

Resumo

Cmtamine is a cationic polypeptide composed by 42 amino acid residues with several pharmacological and biological properties, including the selective ability to enter and kill actively proliferating tumour cells, which led us to propose its use as a theranostic agent for cancer therapy. At the moment, the improvement of crotamine antitumoral efficacy by association with chemotherapeutic adjuvants is envisioned. In the present work, we evaluated the association of crotamine with the antitumoral adjuvant phenotiazine thioridazine (THD). In spite of the clear efficacy of these both compounds as anticancer agents in long-term in vivo treatment of animal model bearing implanted xenograph melanoma tumor, the expected mutual potentiation of the antitumor effects was not observed here. Moreover, this association revealed for the first time the influence of THD on crotamine ability to trigger the hind limb paralysis in mice, and this discovery may represent the first report suggesting the potential involvement of the CNS in the action of this snake polypeptide on the skeletal muscle paralysis, which was classically believed to be essentially limited to a direct action in peripheral tissues as the skeletal muscle. This is also supported by the observed ability of crotamine to potentiate the sedative effects of THD which action was consistently demonstrated to be based on its central action. The better characterization of crotamine properties in CNS may certainly bring important insights for the knowledge needed to pave the way toward the use of this molecule as a theranostic compound in human diseases as cancer. (AU)

• Processo FAPESP: 13/13392-4 - Avaliação do uso dos análogos da crotamina em diagnóstico ou terapia
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/03102-2 - Otimização do tratamento antitumoral com a crotamina por via oral
• Beneficiário: Lucas de Carvalho Porta
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/02413-1 - Validação da crotamina como biomarcador e avaliação do seu potencial uso na terapia de doenças humanas
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/00014-5 - Estudos das potenciais influências alostéricas da tioridazina nos efeitos da crotamina sobre a musculatura esquelética
• Beneficiário: Giovanna Bello Papa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/21381-6 - Validação da "Via Extracelular AMPc-Adenosina" como novo alvo terapêutico para o tratamento de doenças respiratórias crônicas
• Beneficiário: Rosely Oliveira Godinho
• Modalidade de apoio: Auxílio à Pesquisa - Regular