Sweet Bee Venom Triggers Multiple Cell Death Pathways or Spurs Acute Cell Rupture According to Its Concentration in THP-1 Monocytic Leukemia Cells

Abstract

Sweet bee venom (sBV) contains various pharmacologically active components of bee venom (BV), but it is modified via the removal of the harmful substances found in BV. Thus, sBV has been used for pain relief in Oriental medicine but has only recently been applied for the treatment of various diseases. In this study, we examined the pharmacological effects and immunomodulatory functions of sBV in THP-1 monocytic leukemia cells. Growth inhibition and cell death were observed according to the concentration of sBV. However, the rapid collapse of cell cycle distribution was shown at 20 μg/mL sBV treatment, indicating that sBV led to cell death or acute cell rupture according to concentration. sBV administration activated Caspase-9, PARP1, RIPK1, and RIPK3, suggesting that the pharmacological actions of sBV were associated with induction of apoptosis and necroptosis. On the other hand, sBV or LPS administration increased cytokine expression, including IL-1β, and showed synergistic cell death in combinatory treatment conditions. Moreover, combinatory administration of sBV and LPS induced severe damage or death during egg development. This result implies that sBV exhibits both pharmacological and toxic effects depending on its concentration. Therefore, sBV might be a promising therapeutic approach, but optimal concentration should be considered before treatment.

Dual Cytotoxic Responses Induced by Treatment of A549 Human Lung Cancer Cells with Sweet Bee Venom in a Dose-Dependent Manner

“…Our previous study also suggested that distinct pharmacological efficacies for cell death patterns in sBV-treated THP-1 cells were concentration-dependent [ 16 ]. This distinct pharmacological activity might be found in only sBV treatment, and not in other anticancer medication.…”

“…This distinct pharmacological activity might be found in only sBV treatment, and not in other anticancer medication. Low sBV concentrations cause growth inhibition in many cell types, including cancer cells and inflammatory cells; however, high sBV concentrations can cause significant cell death [ 16 ]. This distinct effect of sBV is presumed to occur due to the difference in pharmacological effects around 20 μg/mL in a cell-based experiment.…”

“…This may represent a novel enhancing strategy for hepatocellular carcinoma treatment [ 15 ]. Our recent study on THP-1 monocytic leukemia cells suggested that sBV exhibits both pharmacological and toxic effects depending on its concentration [ 16 ]. Moreover, the pharmacological action of sBV is associated with cell death induction and inflammatory cytokine expression.…”

Pharmacological properties and therapeutic potential of honey bee venom

“…It was discovered that the compounds of BV have anti-cancer activity against MCF7 cells (human breast cancer cells), which cause apoptosis via stimulating caspase - 3 and − 9 or by the discharge of AIF and EndoG from mitochondria ( Moga et al, 2018 ). A recent study has shown that the sweet bee venom revealed cell death of THP-1 (human leukemia monocytic cell line) cells at a concentration of 20 µg/mL ( Ryu et al, 2022 ). Similarly, due to the increased expression of protein of p21 and p53, bee venom also showed anti-tumor efficacy towards pancreatic cancer cell lines ( Zhao et al, 2022 ).…”