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25 January 2022

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

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1
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea
2
Kangwon Center for System Imaging, Kangwon National University, Chuncheon 24341, Korea
3
AJ Research Institute for Integrative Medicine, Seoul 07525, Korea
*
Author to whom correspondence should be addressed.
This article belongs to the Section Molecular Genetics and Genomics

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.

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