Telomerase inhibitors TMPyP4 and thymoquinone decreased cell proliferation and induced cell death in the non-small cell lung cancer cell line LC-HK2, modifying the pattern of focal adhesion

Autor(es)

A.M.B. Garnique ^[1] ; P. Rezende-Teixeira ^[2] ; G.M. MachadoSantelli ^[3]

Afiliação do(s) autor(es)

^[1] Instituto de Ciências Biomédicas, Universidade de São Paulo. Departamento de Biologia Celular e do Desenvolvimento - Brasil

^[2] Instituto de Ciências Biomédicas, Universidade de São Paulo. Departamento de Farmacologia - Brasil

^[3] Instituto de Ciências Biomédicas, Universidade de São Paulo. Departamento de Biologia Celular e do Desenvolvimento - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 56, 2023-10-27.

Resumo

G‐quadruplexes (G4) are structures formed at the ends of telomeres rich in guanines and stabilized by molecules that bind to specific sites. TMPyP4 and thymoquinone (TQ) are small molecules that bind to G4 and have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines, LC‐HK2 (non-small cell lung cancer - NSCLC) and RPE‐1 (hTERT-immortalized), were treated with TMPyP4 (5 μM) and TQ (10 μM). Both inhibitors decreased telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 reduced cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a concentration-dependent manner, increasing the frequency of senescent cells and inducing cell cycle arrest in G1 phase. Thus, the present results showed that TMPyP4 and TQ, although acting as telomerase inhibitors, had a broader effect on other signaling pathways and processes in cells, differing from each other. However, they act both on malignant and immortalized cells, and further studies are needed before their anti-cancer potential can be considered. (AU)

• Processo FAPESP: 15/17177-6 - Abordagem integrada na prospecção sustentável de produtos naturais marinhos: da diversidade a substâncias anticâncer
• Beneficiário: Leticia Veras Costa Lotufo
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático