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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 24; p. 4498
• Main Authors: M Franco, Yollanda E, Y Okubo, Marcia, D Torre, Adriana, P Paiva, Paula, N Rosa, Marcela, O Silva, Viviane A, M Reis, Rui, T G Ruiz, Ana L, M Imamura, Paulo, de Carvalho, João E, B Longato, Giovanna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.12.2019; MDPI
• Subjects: Apoptosis; Apoptosis - drug effects; Aquatic plants; BAX protein; Biotechnology; Brain cancer; Breast cancer; Cancer therapies; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cervical cancer; Cervix; Cyclin D1; Cyclin-dependent kinase; Cytotoxicity; Deoxyribonucleic acid; Depolarization; Diterpenes; Diterpenes - chemistry; Diterpenes - pharmacology; DNA; Evaluation; G1 phase; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Glioma cells; Hepatocellular carcinoma; Humans; Hydrogen peroxide; Inflammation; Kinases; Lung cancer; Medical prognosis; Membrane potential; Mitochondria; Mortality; Natural products; Oral cancer; Organic chemistry; Phosphorylation - drug effects; Prostate; Protein kinase; Proteins; Reactive Oxygen Species - chemistry; Rhizomes; Tumor cell lines; Tumors; Zingiberaceae - chemistry; Brazil; natural products; apoptosis; glioblastoma; cell cycle arrest; coronarin D
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24244498

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 , 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.