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.

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine’s binding site on β-tubulin were performed, suggesting (−)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

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