Review

.2020 Jan 21;12(2):66.

doi: 10.3390/toxins12020066.

Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

Andreas Aufschnaiter¹, Verena Kohler², Shaden Khalifa², Aida Abd El-Wahed^{3 4 5}, Ming Du⁶, Hesham El-Seedi^{4 5 7}, Sabrina Büttner^{2 8}

Affiliations

¹ Department of Biochemistry and Biophysics, Stockholm University, Svante Arrheniusväg 16, 106 91 Stockholm, Sweden.
² Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 106 91 Stockholm, Sweden.
³ Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, 12627 Giza, Egypt.
⁴ Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 751 23 Uppsala, Sweden.
⁵ Department of Chemistry, Faculty of Science, Menoufia University, 32512 Shebin El-Kom, Egypt.
⁶ School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116024, China.
⁷ International Research Center for Food nutrition and safety, Jiangsu University, Zhenjiang 212013, China.
⁸ Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, 8010 Graz, Austria.

PMID:31973181
PMCID: PMC7076873
DOI: 10.3390/toxins12020066

Review

Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

Andreas Aufschnaiter et al. Toxins (Basel).2020.

.2020 Jan 21;12(2):66.

doi: 10.3390/toxins12020066.

Authors

Andreas Aufschnaiter¹, Verena Kohler², Shaden Khalifa², Aida Abd El-Wahed^{3 4 5}, Ming Du⁶, Hesham El-Seedi^{4 5 7}, Sabrina Büttner^{2 8}

Affiliations

¹ Department of Biochemistry and Biophysics, Stockholm University, Svante Arrheniusväg 16, 106 91 Stockholm, Sweden.
² Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 106 91 Stockholm, Sweden.
³ Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, 12627 Giza, Egypt.
⁴ Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 751 23 Uppsala, Sweden.
⁵ Department of Chemistry, Faculty of Science, Menoufia University, 32512 Shebin El-Kom, Egypt.
⁶ School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116024, China.
⁷ International Research Center for Food nutrition and safety, Jiangsu University, Zhenjiang 212013, China.
⁸ Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, 8010 Graz, Austria.

PMID:31973181
PMCID: PMC7076873
DOI: 10.3390/toxins12020066

Abstract

Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent years, multifactorial diseases such as cancer, rheumatoid arthritis and neurodegenerative diseases remain major healthcare issues at present. Although pure bee venom, apitoxin, is mostly described to mediate anti-inflammatory, anti-arthritic and neuroprotective effects, its primary component melittin may represent an anticancer therapeutic. In this review, we approach the possibilities and limitations of apitoxin and its components in the treatment of these multifactorial diseases. We further discuss the observed unspecific cytotoxicity of melittin that strongly restricts its therapeutic use and review interesting possibilities of a beneficial use by selectively targeting melittin to cancer cells.

Keywords: apamin; apitoxin; bee venom; cancer; melittin; neurodegeneration; phospholipase A2; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

**Figure 1**
Potential application of melittin in cancer therapy. While specific cytotoxic effects of melittin against cancer cells have been reported, melittin has also been shown to mediate unspecific toxicity towards healthy cells (illustrated as question mark). However, chemical modification, e.g., by conjugation of melittin to avidin, which is cleaved and activated by cancer cell-specific matrix metalloproteinase 2 (MMP2), or cancer cell-directed targeting of melittin with nanocarriers might be used to overcome this unspecific toxicity.

**Figure 2**
Postulated therapeutic effects of bee venom and melittin against neuroinflammation in diverse neurodegenerative diseases. The tumour necrosis factor α (TNF-α) pathway (illustrated in a simplified way) is an important mechanism by which inflammatory processes are activated and is overstimulated in various neurodegenerative disorders (red arrows), including Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). The protective effects of bee venom and melittin (shown with black arrows for activation and black bar-headed arrows for repression) are controversial (illustrated as question marks in the figure). Further research is required to characterize these effects and to evaluate, whether they are caused by a reduction in neuroinflammation or by other mechanisms. TNFR1/2 = Tumour necrosis factor receptor 1/2; IL-1α = Interleukin 1α; NF-κB = Nuclear factor kappa-light chain enhancer of activated B cells.

**Figure 3**
Proposed therapeutic effects of bee venom and melittin against inflammation and pain in rheumatoid arthritis. The protective effects of bee venom and melittin (shown as black arrows for activation and black bar-headed arrows for repression) are controversial (illustrated as question marks in the figure), and further investigation is needed to assess the usability of apitoxin and/or melittin as a novel treatment strategy in this multifactorial disease. NF-κB = Nuclear factor kappa light chain enhancer of activated B cells.

See this image and copyright information in PMC

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Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

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Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

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Conflict of interest statement

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