Abstract
BackgroundThe involvement of MMP-2 and MMP-9 in the pathogenesis of various kinds of cancers including glioblastoma is well documented. The evaluation of the anticancer potential of honey bee (Apis mellifera) venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study.Methods8-MG-BA and GAMG human primary glioblastoma cell lines vs. HT-22 mouse hippocampal neuronal cells were applied for the study. The BV dose (0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, and 5.0 μg/ml) and time-dependent (24, 48, 72 h) cytotoxicity was evaluated with the tetrazolium-based colorimetric assay (MTT test). MMP-2 and MMP-9 activities in the cell culture medium under different BV concentrations were determined by gelatin zymography.ResultsA dose and time-dependent BV effect on cytotoxicity of both glioblastoma cell lines and hippocampus line was observed. The weakest, but statistically important effect was exerted by BV on HT-22 cells. The greatest cytotoxic effect of BV was observed on the 8-MG-BA line, where a statistically significant reduction in viability was observed at the lowest BV dose and the shortest incubation time. The reduction of both gelatinases secretion was observed at 8-MG-BA and GAMG lines without significant effect of HT-22 cell line.ConclusionIn vitro studies indicate that BV has both cytotoxic and inhibitory effects on the secretion of MMP-2 and MMP-9 in selected lines of glioma, suggesting anticancer properties of BV.
Highlights
The classification of gliomas includes four grades, with grade four glioblastoma representing the most malignant type and known as glioblastoma multiforme (GBM) (Atiq and Parhar, 2020)
In Bee venom (BV) samples collected from honey bees (Apis mellifera) in Poland, the content of the mentioned substances has been amounted to 61.15–70.15% for melittin, 11.24– 15.05% for Phospholipase A2 (PLA2) and 2.09–4.18% for apamine (Rybak-Chmielewska and Szczesna, 2006)
The most significant timedependent effect of BV was observed on GAMG cells, where the increase of incubation time from 24 to 72 h decreased the IC50 from 1.519 to 0.274 ng/ml
Summary
The classification of gliomas includes four grades, with grade four glioblastoma representing the most malignant type and known as glioblastoma multiforme (GBM) (Atiq and Parhar, 2020). Bee Venom in Glioblastoma research, it remains a great therapeutic challenge. Current treatment methods include surgical tumor resection with chemotherapy and radiotherapy thereafter. Even with advanced surgical techniques such as e.g., fluorescence-guided resection, the complete removal of cancer cells is almost impossible because tumor cells located at the edges of tumors in perivascular niches remain in most cases (Atiq and Parhar, 2020). In BV samples collected from honey bees (Apis mellifera) in Poland, the content of the mentioned substances has been amounted to 61.15–70.15% (average 64.40%) for melittin, 11.24– 15.05% (average 13.00%) for PLA2 and 2.09–4.18% (average 3.10%) for apamine (Rybak-Chmielewska and Szczesna, 2006). The evaluation of the anticancer potential of honey bee (Apis mellifera) venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study
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