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Open AccessArticle

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

1
Research Laboratory in Molecular Pharmacology of Bioactive Compounds. São Francisco University, Bragança Paulista 12916–900, SP, Brazil
2
Posgraduate program in Health Science, São Francisco University, Bragança Paulista 12916–900, SP, Brazil
3
Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas–UNICAMP, Paulínia 13148–218, SP, Brazil
4
Posgraduate program in dentistry, Piracicaba Dental School, University of Campinas, Piracicaba 13 414–903, SP, Brazil
5
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14.784–400, SP, Brazil
6
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710–057 Braga, Portugal
7
ICVS/3B’s–PT Government Associate Laboratory, 4710–057 Braga, Portugal
8
Faculty of Pharmaceutical Sciences, University of Campinas, UNICAMP, Campinas 13081–970, SP, Brazil
9
Institute of Chemistry, University of Campinas–UNICAMP, P.O. Box 6154, Campinas 13083–970, SP, Brazil
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Roberto Fabiani
Molecules 2019, 24(24), 4498; https://doi.org/10.3390/molecules24244498
Received: 25 October 2019 / Revised: 18 November 2019 / Accepted: 21 November 2019 / Published: 9 December 2019
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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. View Full-Text
Keywords: coronarin D; glioblastoma; apoptosis; cell cycle arrest; natural products coronarin D; glioblastoma; apoptosis; cell cycle arrest; natural products
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MDPI and ACS Style

M. Franco, Y.E.; Y. Okubo, M.; D. Torre, A.; P. Paiva, P.; N. Rosa, M.; O. Silva, V.A.; M. Reis, R.; T. G. Ruiz, A.L.; M. Imamura, P.; de Carvalho, J.E.; B. Longato, G. Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line. Molecules 2019, 24, 4498.

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