ARTICLE | doi:10.20944/preprints202210.0080.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: cannabidiol; electric cell-substrate impedance sensing; oral cancer
Online: 7 October 2022 (14:32:52 CEST)
Cannabidiol (CBD) is an active diterpenoid compound that is extracted from the leaves and stem of Cannabis sativa. Previous studies show that CBD is a non-psychotropic compound with significant anti-cancer effects. This study determines its cytotoxic effect on oral cancer cells and OECM1 cells and compares the outcomes with a chemotherapeutic drug, cisplatin. This study determines the effect of CBD on the viability, apoptosis, morphology and migration of OECM1 cells. Electric cell-substrate impedance sensing (ECIS) is used to measure the change in cell impedance for cells that are treated with a series concentration of CBD for 24 hours. AlamarBlue and annexin V/7-AAD staining assays show that CBD has a cytotoxic effect on cell viability and induces cell apoptosis. ECIS analysis shows that CBD decreases the overall resistance and morphological parameters at 4 kHz in a concentration-dependent manner. There is a significant reduction in the wound-healing recovery rate for cells that are treated with 30 μM CBD. This study demonstrates that ECIS can be used for in vitro screening of anticancer drugs and is more sensitive, functional and comprehensive than traditional biochemical assays. CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer
ARTICLE | doi:10.20944/preprints201905.0374.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Keywords: Tumor microenvironment (TME), glioblastoma multiforme (GBM), GBM- associated macrophages (GAMs), exosomes, oncomiR-21, STAT3 inhibitor.
Online: 31 May 2019 (08:18:33 CEST)
Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.