Bee Venom as Adjuvant Therapy

Dr. Weeks’ Comment: Bee venom therapy has a glorious history in many cultures. I first learned that the beehive is a fabulous pharmacy before I went to medical school and, while in medical school, I founded the American Apitherapy Society (AAS) with my friend and mentor – master Apitherapist Charlie Mraz. As president of AAS, I led a group of doctors to China in 1993 and subsequently convened international forums on apitherapy which fostered improved international relations and scientific breakthroughs. Only in the USA is the medicinal aspects of the glorious honey bee ignored. Scientists in Israel, throughout the Arab middle east countries, China, Egypt – all study clinical applications of apitherapy. Just to PUBMED and search the term “bee venom cancer” and find hundreds of peer reviwed scientific articles. On powerful component of bee venom mellitin, in particular (see below) is used as an adjuvant agent to facilitate the efficacy of other conventional drugs. To learn more about the medicinal aspects of the honey bee (apitherapy) watch this video of a lecture on Apitherapy.

Process of inducing pores in membranes by melittin

Ming-Tao Lee, Tzu-Lin Sun, Wei-Chin Hung, and Huey W. Huang PNAS August 12, 2013  https://doi.org/10.1073/pnas.1307010110 Edited by Donald M. Engelman, Yale University, New Haven, CT.

SOURCE

Melittin is a prototype of the ubiquitous antimicrobial peptides that induce pores in membranes. It is commonly used as a molecular device for membrane permeabilization. Even at concentrations in the nanomolar range, melittin can induce transient pores that allow transmembrane conduction of atomic ions but not leakage of glucose or larger molecules. At micromolar concentrations, melittin induces stable pores allowing transmembrane leakage of molecules up to tens of kilodaltons, corresponding to its antimicrobial activities. Despite extensive studies, aspects of the molecular mechanism for pore formation remain unclear. To clarify the mechanism, one must know the states of the melittin-bound membrane before and after the process. By correlating experiments using giant unilamellar vesicles with those of peptide-lipid multilayers, we found that melittin bound on the vesicle translocated and redistributed to both sides of the membrane before the formation of stable pores. Furthermore, stable pores are formed only above a critical peptide-to-lipid ratio. The initial states for transient and stable pores are different, which implies different mechanisms at low and high peptide concentrations. To determine the lipidic structure of the pore, the pores in peptide–lipid multilayers were induced to form a lattice and examined by anomalous X-ray diffraction. The electron density distribution of lipid labels shows that the pore is formed by merging of two interfaces through a hole. The molecular property of melittin is such that it adsorbs strongly to the bilayer interface. Pore formation can be viewed as the bilayer adopting a lipid configuration to accommodate its excessive interfacial area.

AND HERE ARE OTHER ARTICES about the benefits of MELLITIN

Melittin: a lytic peptide with anticancer properties

G Gajski, V Garaj-Vrhovac – Environmental toxicology and pharmacology, 2013 – Elsevier

Melittin (MEL) is a major peptide constituent of bee venom that has been proposed as one of the upcoming possibilities for anticancer therapy. Recent reports point to several mechanisms of MEL cytotoxicity in different types of cancer cells such as cell cycle alterations, effect on proliferation and/or growth inhibition, and induction of apoptotic and necrotic cell death trough several cancer cell death mechanisms, including the activation of caspases and matrix metalloproteinases. Although cytotoxic to a broad spectrum of tumour cells, the peptide is also toxic to normal cells. Therefore its therapeutic potential cannot be achieved without a proper delivery vehicle which could be overcome by MEL nanoparticles that possess the ability to safely deliver significant amount of MEL intravenously, and to target and kill tumours. This review paper summarizes the current knowledge and brings latest research findings on the anticancer potential of this lytic peptide with diverse functions.

Melittin prevents liver cancer cell metastasis through inhibition of the Rac1‐dependent pathway

S Liu, M Yu, Y He, L Xiao, F Wang, C Song, S Sun… – …, 2008 – Wiley Online Library

Melittin, a water‐soluble toxic peptide derived from bee venom of Apis mellifera was reported to have inhibitory effects on hepatocellular carcinoma (HCC). However, its role in antimetastasis and the underlying mechanism remains elusive. By utilizing both HCC cell …

Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

M Jo, MH Park, PS Kollipara, BJ An, HS Song… – Toxicology and applied …, 2012 – Elsevier

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited …

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

I RadyIA Siddiqui, M Rady, H Mukhtar – Cancer letters, 2017 – Elsevier

Melittin (MEL), a major peptide component of bee venom, is an attractive candidate for cancer therapy. This agent has shown a variety of anti-cancer effects in preclinical cell culture and animal model systems. Despite a convincing efficacy data against variety of …

Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies

PJ Russell, D Hewish, T Carter, K Sterling-Levis… – Cancer Immunology …, 2004 – Springer

Abstract Background: Monoclonal antibodies (MAbs) can target therapy to tumours while
minimising normal tissue exposure. Efficacy of immunoconjugates containing peptide 101, designed around the first 22 amino acids of bee venom, melittin, to maintain the amphipathic …

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Dr. Weeks’ Comment: Bee venom therapy has a glorious history in many cultures. I first learned that the beehive is a fabulous pharmacy before I went to medical school and, while in medical school, I founded the American Apitherapy Society (AAS) with my friend and mentor – master Apitherapist Charlie Mraz. As president of AAS,…
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