Biology subjects

Molina-Holgado, F.

Publications and source records attributed to Molina-Holgado, F..

2 recordsLinked to original sources

bioRxiv2024

DIFFERENTIAL ANTIPROLIFERATIVE EFFECTS OF CANNABIDIOL (CBD) IN THE CORE AND INFILTRATIVE BOUNDARY OF HUMAN GLIOBLASTOMA CELLS

BackgroundWe have previously reported that the brain cannabinoid signalling pathways regulates in the isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core and infiltrative boundary tumor cell proliferation. To uncover the mechanism behind these effects we have investigated the possible antitumoral actions of cannabidiol (CBD) in the tumour core cells (U87) and the Glioma Invasive Margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. MethodsMonolayer of GBM cells cultures were treated with increasing concentrations of CBD, Temozolomide (TMZ), Carmustine (BCUN), Fluoxetine, Doxorubicine (DOX) or vehicle. After treatment, cell viability was assessed using an MTT kit assay to evaluate mitochondrial activity/cell proliferation, cytotoxicity was evaluated by LDH release. In addition, we have investigated the effects of the CBD alone or in combination with the above drugs on the autophagic cell death, unfold protein response (UPR) mitochondrial response and release of proinflammatory cytokines. SummaryThis study highlights the potential therapeutic relevance of CBD in combination with other FDA-approved drugs against glioblastoma. We observed strong synergism between CBD and TMZ, FX, and DOXO in reducing U87-MG cell viability in vitro, with even stronger synergy between CBD and TMZ in GIN-8 cells. Our preliminary data identify CBD as a potential anti-neoplastic drug in both core and invasive margin cells. Given the heterogeneity of glioblastoma, further studies will elucidate the molecular mechanisms underlying CBD observed anti-tumoral actions and determine whether it can potentially be used in the future as an addition to current therapies.

cancer biology↗

bioRxiv2021

Transcription Profile And Pathway Analysis Of The Endocannabinoid Receptor Inverse Agonist AM630 In The Core And Infiltrative Boundary Of Human Glioblastoma Cells

BackgroundWe have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumor cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. ResultsThe core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists. ConclusionOur results highlight the different responsiveness of the core and invasive margin cells. Taken together, whilst our findings identify AM630 as an anti-neoplastic drug, showing a high correlation with known anti-proliferative drugs, we find distinct drug sensitivies of the infiltrative margin relative to contrast-enhanced core regions of GBM upon which failed molecular targeted therapies to date have been predicated.

cancer biology↗