Potentiation of a novel palladium (II) complex lethality with bee venom on the human T-cell acute lymphoblastic leukemia cell line (MOLT-4)

Abstract

BackgroundAlthough honeybee venom (BV) has been reported to induce apoptosis in different types of cancerous cells, its synergistic effects with customary anti-cancer drugs remain largely unknown. In the present study, we evaluated the cytotoxic effect of BV alone (as a natural product) and the synergistic cytological effects of this component in combination with [Pd (bpy) (Pi-Pydtc)]NO3 – a novel palladium complex on human T-cell lymphoblastic leukemia cells. To investigate the cytotoxic effect of the BV alone and in combination with palladium complex on MOLT-4 cells MTT assay was performed. In order to determine the apoptotic effects of BV separately and in combination with Pd (II) complex on these cells and its ability to induce apoptosis, morphological examination, flowcytometric analysis and caspase-3 colorimetric assay were done.ResultsWe found that BV induced morphological changes, namely nuclear shrinkage, and inhibited MOLT-4 cell proliferation; both effects were dose- and time-dependent. Flow cytometry by Annexin-V antibody demonstrated that BV induced apoptosis in MOLT-4 cells. Furthermore, BV induced apoptosis independently of caspase-3 in these cells. In addition, we proved a clear synergistic effect of BV on [Pd (bpy) (Pi-Pydtc)]NO3. The apoptotic pathway activated by BV in combination with Pd complex was caspase-3-dependent.ConclusionsThese observations provide an explanation for the anti-proliferative properties of BV, and suggest that this agent may be useful for treating lymphoblastic leukemia alone or in combination with chemotherapy drugs pending further investigations on animal models as preclinical tests.

Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin

“…Other authors also noticed joint effects of BV and MEL on the cytotoxicity of cytostatic drugs in different cancer cells (Oršolić 2009;Alizadehnohi et al 2012;Safaeinejad et al 2013;Choi et al 2014). Oršolić (2009) observed potentiation of BV cytotoxicity with the DNA-damaging drug bleomycin on HeLa and Chinese hamster lung fibroblast V79 cells.…”

“…Alizadehnohi et al (2012) also showed that effects of cDDP in ovarian cancerous cDDP-resistant A2780cp cells could be enhanced by the addition of a non-lethal dose of BV. Most recently, Safaeinejad et al (2013) evaluated the synergistic cytological effects of BV and novel palladium (II) complex [Pd (bpy) (Pi-Pydtc)]NO 3 on human T-cell lymphoblastic leukemia MOLT-4 cells. They also found a clear synergistic effect of BV on a Pd complex and the apoptotic pathway activated by BV in combination with Pd complex was caspase-3-dependent.…”

Antimicrobial Properties of Apis mellifera’s Bee Venom

“…However, using BV and melittin induces extensive hemolysis and toxicity of the cells, a severe side effect that limits their future development and clinical application. Ongoing research is addressing practical issues including standardization, toxicity, and stability [97][98][99][100].…”