Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line

Autor(es):Mostrar menos -

Franco, Yollanda E. M. ^{[1, 2]} ; Okubo, Marcia Y. ^{[3, 4]} ; Torre, Adriana D. ^[4] ; Paiva, Paula P. ^[4] ; Rosa, Marcela N. ^[5] ; Silva, Viviane A. O. ^[5] ; Reis, Rui M. ^{[5, 6, 7]} ; Ruiz, Ana L. T. G. ^{[3, 8]} ; Imamura, Paulo M. ^[9] ; de Carvalho, Joao E. ^{[3, 8]} ; Longato, Giovanna B. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Sao Francisco Univ, Res Lab Mol Pharmacol Bioact Cpds, BR-12916900 Braganca Paulista, SP - Brazil

^[2] Sao Francisco Univ, Posgrad Program Hlth Sci, BR-12916900 Braganca Paulista, SP - Brazil

^[3] Univ Estadual Campinas, Piracicaba Dent Sch, Posgrad Program Dent, BR-13414903 Piracicaba, SP - Brazil

^[4] Univ Estadual Campinas, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, UNICAMP, BR-13148218 Paulinia, SP - Brazil

^[5] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP - Brazil

^[6] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga - Portugal

^[7] ICVS 3BsPT Govt Associate Lab, P-4710057 Braga - Portugal

^[8] Univ Estadual Campinas, Fac Pharmaceut Sci, UNICAMP, BR-13081970 Campinas, SP - Brazil

^[9] Univ Estadual Campinas, Inst Chem, UNICAMP, POB 6154, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 24, n. 24 DEC 2019.
• Citações Web of Science: 0

Resumo

Glioblastoma (GBM) is the most frequent and highest-grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti-cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U-251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U-251 and provide a basis for further investigation on its antineoplastic activity on brain cancer. (AU)

• Processo FAPESP: 16/06137-6 - Bioprospecção de compostos naturais e derivados bioativos com potencial atividade anticâncer: ensaios in vitro/in vivo e investigação do mecanismo de ação.
• Beneficiário: Giovanna Barbarini Longato
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/06636-7 - Atividade antiproliferativa in vitro da Coronarina-D
• Beneficiário: Márcia Yumi Okubo
• Linha de fomento: Bolsas no Brasil - Mestrado