dc.contributor.author | Sanchez-Martin, Vanesa | |
dc.contributor.author | Jimenez-Garcia, Lidia | |
dc.contributor.author | Herranz, Sandra | |
dc.contributor.author | Luque, Alfonso | |
dc.contributor.author | Acebo, Paloma | |
dc.contributor.author | Amesty, Ángel | |
dc.contributor.author | Estévez-Braun, Ana | |
dc.contributor.author | de Las Heras, Beatriz | |
dc.contributor.author | Hortelano, Sonsoles | |
dc.date.accessioned | 2020-03-03T13:09:53Z | |
dc.date.available | 2020-03-03T13:09:53Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Front Pharmacol. 2019 Sep 3;10:935. | es_ES |
dc.identifier.issn | 1663-9812 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9166 | |
dc.description.abstract | α-Hispanolol (α-H) is a labdane diterpenoid that has been shown to induce apoptosis in several human cancer cells. However, the effect of α-H in human glioblastoma cells has not been described. In the present work, we have investigated the effects of α-H on apoptosis, migration, and invasion of human glioblastoma cells with the aim of identifying the molecular targets underlying its mechanism of action. The results revealed that α-H showed significant cytotoxicity against human glioma cancer cell lines U87 and U373 in a concentration- and time-dependent manner. This effect was higher in U87 cells and linked to apoptosis, as revealed the increased percentage of sub-G1 population by cell cycle analysis and acquisition of typical features of apoptotic cell morphology. Apoptosis was also confirmed by significant presence of annexin V-positive cells and caspase activation. Pretreatment with caspase inhibitors diminishes the activities of caspase 8, 9, and 3 and maintains the percentage of viable glioblastoma cells, indicating that α-H induced cell apoptosis through both the extrinsic and the intrinsic pathways. Moreover, we also found that α-H downregulated the anti-apoptotic Bcl-2 and Bcl-xL proteins and activated the pro-apoptotic Bid and Bax proteins. On the other hand, α-H exhibited inhibitory effects on the migration and invasion of U87 cells in a concentration-dependent manner. Furthermore, additional experiments showed that α-H treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase MMP-2 and MMP-9 and increased the expression of TIMP-1 inhibitor, probably via p38MAPK regulation. Finally, xenograft assays confirmed the anti-glioma efficacy of α-H. Taken together, these findings suggest that α-H may exert anti-tumoral effects in vitro and in vivo through the inhibition of cell proliferation and invasion as well as by the induction of apoptosis in human glioblastoma cells. This research describes α-H as a new drug that may improve the therapeutic efficacy against glioblastoma tumors. | es_ES |
dc.description.sponsorship | This study was supported by grant PI11/00036, PI14/00055, and PI17/00012 from the FIS, MPY 1410/09 from ISCIII and Spanish Ministry of Health (Instituto de Salud Carlos III; RD12/0036/0059) to SoH and by grants IERPY 1149/16 and IERPY-M 389/18 to AL. L JG was supported by FIS (FI12/00340). SaH was supported by IERPY 1149/16 from ISCIII. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Frontiers Media | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Apoptosis | es_ES |
dc.subject | Caspases | es_ES |
dc.subject | Glioblastoma | es_ES |
dc.subject | Matrix metalloproteinases | es_ES |
dc.subject | Migration | es_ES |
dc.subject | α-hispanolol | es_ES |
dc.title | α-Hispanolol Induces Apoptosis and Suppresses Migration and Invasion of Glioblastoma Cells Likely via Downregulation of MMP-2/9 Expression and p38MAPK Attenuation | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 31551765 | es_ES |
dc.format.volume | 10 | es_ES |
dc.format.page | 935 | es_ES |
dc.identifier.doi | 10.3389/fphar.2019.00935 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.3389/fphar.2019.00935 | es_ES |
dc.identifier.journal | Frontiers in pharmacology | es_ES |
dc.repisalud.centro | ISCIII::Instituto de Investigación de Enfermedades Raras | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI11/00036 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI14/00055 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI17/00012 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/MPY 1410/09 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0036/0059 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/IERPY-M 389/18 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FI12/00340 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/IERPY 1149/16 | es_ES |
dc.rights.accessRights | open access | es_ES |