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Isolated Components From Spider Venom Targeting Human Glioblastoma Cells and Its Potential Combined Therapy With
Marcus Caballero1,2, Natalia Barreto1,2, Amanda Pires Bonfanti1,2
1Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.
Frontiers in Molecular Biosciences
|April 1, 2022
Summary
Components from the Phoneutria nigriventer spider venom (PnV) show promise for glioblastoma treatment. Specific PnV fractions, SF3 and SF4, demonstrated significant antineoplastic effects and synergistic potential with rapamycin.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Glioblastomas (GBs) are aggressive brain tumors with poor prognosis, representing over 50% of glioma mortality.
- Peptide-based antineoplastic therapies, particularly those derived from spider venoms, offer a promising avenue for cancer treatment.
- Previous research indicated cytotoxic effects of Phoneutria nigriventer spider venom (PnV) on glioblastoma cells.
Purpose of the Study:
- To isolate and identify specific PnV components with antineoplastic activity against glioblastoma.
- To evaluate the effects of different PnV fractions and metabolic conditions on glioblastoma cell viability, proliferation, and death.
- To investigate the potential synergistic effects of PnV components with mTOR inhibitors like rapamycin.
Main Methods:
- Human glioblastoma (NG97) cells were treated with purified PnV fractions (F1, F2, F3) and subsequently with subfractions (SF1-SF11).
- Cell viability (MTT assay), proliferation (CFSE assay), apoptosis (Annexin V/PI staining), and cell cycle progression (PI staining) were assessed.
- Synergistic effects were evaluated by combining PnV subfractions with rapamycin, an mTOR inhibitor.
Main Results:
- PnV fractions F1 and F2, particularly at low concentrations and short exposure times, exhibited significant cytotoxic effects.
- Subfractions SF3 and SF4 demonstrated the most potent antineoplastic activity.
- Combination therapy with SF3/SF4 and rapamycin resulted in a significant reduction in glioblastoma cell viability, exceeding effects of either agent alone.
Conclusions:
- Components within PnV subfractions SF3 and SF4 show potential as prototypes for novel glioblastoma therapeutics.
- These PnV components may be effective in combination therapy with rapamycin or similar mTOR-inhibiting agents.
- Further research is warranted to characterize, synthesize, and evaluate the preclinical efficacy and safety of these PnV-derived compounds.
