Anticancer potential of bee venom and propolis combined treatment on human breast adenocarcinoma cell line [MCF-7]

Backgrounds: Natural remedies were used for cancer treatments, particular breast cancer. Also, the consumption of food products containing high amount of flavonoids and antioxidants had reported to lower the risk of various cancers. Bee venom [BV] and propolis were produced by honey bee. They were characterized by naturopathic formulation, affordability and containing high amount of antioxidants. Moreover, they were used safely since ancient times globally. Although that, there is no information about the synergistic or antagonistic anticancer effects of their combination. This study was designed to evaluate cytotoxic and pro-apoptotic effects of BV, propolis, and their combination on breast cancer [MCF-7] cells

Materials and Methods: As preliminary study, MCF-7 cells were treated with BV [5, 10, and 20micro g/ml] and propolis [50, 150, and 450micro g/ml] to specify the desired combination doses of each treatment with no anticancer effect individually. Consequently, doses of [5micro g/ml BV+ 50micro g/ml propolis and 5micro g/ml BV+ 150micro g/ml propolis] were chosen to evaluate the possible synergistic anticancer potential between them. All groups in this study were examined at 2, 4, and 12 hours intervals. The morphological changes were evaluated by acridine orange/ ethidium bromide dual fluorescent staining and Giemsa staining to reveal the formation of apoptotic bodies or nuclear condensation and cytoplasmic blebbing, respectively. DNA fragmentation assay was also carried out to record the reduction in DNA content and apoptosis. Bcl-2 expression, cytoplasmic anti-apoptotic marker, was used to prove the apoptotic properties, and autophagic cell death by florescent microscopy was evaluated also

Results: Morphological observation by inverted and florescent microscopy revealed apoptotic cell death under exposure to BV [10 and 20micro g/ml] and propolis [450micro g/ml]. On the other hand, the results of combined treatments revealed significant morphological alterations after fluorescent and Giemsa staining. Apoptotic DNA fragmentation was clearly observed and Bcl-2 recoded significant down regulation which proved the apoptotic properties of combined treatments. Additionally, autophagic degradation results also supported the occurrence of stress on treated cells leading finally to cell death. All results of powerful anticancer potential were obvious among all combined-treated groups in dose and time dependent manner. This clear that, the combined treatments have possible synergistic effect which, propose it as potential candidates to be used in development of chemotherapy

Bee venom stimulates human melanocyte proliferation, melanogenesis, dendricity and migration

Pigmentation may result from melanocyte proliferation, melanogenesis, migration or increases in dendricity. Recently, it has been reported that secreted phospholipase A2(sPLA2) known as a component of bee venom (BV), stimulates melanocyte dendricity and pigmentation. BV has been used clinically to control rheumatoid arthritis and to ameliorate pain via its anti-inflammatory and antinociceptive properties. Moreover, after treatment with BV, pigmentation around the injection sites was occasionally observed and the pigmentation lasted a few months. However, no study has been done about the effect of BV on melanocytes. Thus, in the present study, we examined the effect of BV on the proliferation, melanogenesis, dendricity and migration in normal human melanocytes and its signal transduction. BV increased the number of melanocytes dose and time dependently through PKA, ERK, and PI3K/Akt activation. The level of cAMP was also increased by BV treatment. Moreover, BV induced melanogenesis through increased tyrosinase expression. Furthermore, BV induced melanocyte dendricity and migration through PLA2activation. Overall, in this study, we demonstrated that BV may have an effect on the melanocyte proliferation, melanogenesis, dendricity and migration through complex signaling pathways in vitro, responsible for the pigmentation. Thus, our study suggests a possibility that BV may be developed as a therapeutic drug for inducing repigmentation in vitiligo skin.

Envenenamiento por picaduras de abeja / Poisoning by bee sting

Dentro de las patologías humanas producidas por animales con la capacidad de inocular veneno, las picaduras de abeja producen el mayor número de accidentes por animales en muchos países, superando a menudo en mortalidad a los producidos por serpientes, escorpiones y arañas. El cuadro clínico por la picadura de estos himenópteros puede consistir en fenómenos alérgicos o en cuadros de envenenamiento. Estos últimos se producen por el ataque de enjambres constituyendo un hecho grave que puede comprometer la vida. En el sujeto envenenado pueden observarse hemólisis, rabdomiólisis e insuficiencia renal, que junto a otras alteraciones sistémicas pueden conducir a la muerte. El conocimiento de los acontecimientos fisiopatológicos que se producen ante los ataques masivos de abejas es de suma importancia para el personal de salud dado que hasta la fecha no existen antivenenos que hayan demostrado tener eficacia clínica comprobada. En esta revisión se consideran los aspectos biológicos de las abejas y de la composición de su veneno relacionado con la ocurrencia y severidad de los accidentes, así como datos epidemiológicos de utilidad para enfrentarse a este tipo de cuadro.

Among the human pathologies produced by venomous animals, bee stings constitute the largest number of accidents in several countries, exceeding the mortality rate caused by other venomous animals such as snakes, spiders or scorpions. The clinical picture after the bee sting may include anaphylaxis or poisoning. The latter is produced by massive attacks and is a serious problem that may put the patient's life at risk. People that are poisoned display hemolysis, rhabdomiolysis and acute renal failure that together with other systemic failures can bring about death. The knowledge of the physiopathological mechanisms involved in the massive attack of bees is crucial for health care professionals as to date we do not ha ve antivenoms with proven clinical efficacy. In this review we include the bee's biological aspects, venom composition and its relation with the occurrence and severity of accidents as well as epidemiological data that can be useful for this type of accidents.

Cardiovascular profile after intravenous injection of Africanized bee venom in awake rats

As manifestações causadas por picadas de abelhas africanizadas dependem da sensibilidade da vítima e da toxicidade do veneno. Estudos anteriores em nosso laboratório mostraram alterações cardíacas e necrose tubular aguda (NTA) nos rins de ratos inoculados com veneno de abelhas africanizadas (VAA). O objetivo do presente estudo foi avaliar as alterações na pressão arterial média (PAM) e na freqüência cardíaca (FC) num período de 24 horas após a inoculação de VAA em ratos mantidos acordados. Uma redução significante na FC basal e na PAM ocorreu imediatamente após a inoculação de VAA nos animais experimentais. A FC voltou aos níveis basais 2 min após a inoculação do VAA e permaneceu nestes valores durante o restante do experimento, enquanto que a PAM voltou aos níveis basais 10 min após a inoculação e permaneceu nestes níveis pelas próximas 5 horas. Por outro lado, a PAM apresentou uma nova diminuição significante nas 7ª e 8ª horas retornando aos níveis basais na 24ª hora. A queda na PAM nos animais inoculados com VAA deve contribuir na patogênese da NTA observada nos rins destes animais. Provavelmente a queda da PAM seja multifatorial, além das alterações cardíacas já demonstradas, os próprios componentes do veneno e/ou substâncias liberadas no organismo podem atuar na resistência vascular, contribuindo para alterações na pressão arterial.

General pharmacological profiles of bee venom and its water soluble fractions in rodent models

Recently, the antinociceptive and anti-inflammatory efficacy of bee venom (BV, Apis mellifera) has been confirmed in rodent models of inflammation and arthritis. Interestingly, the antinociceptive and anti-inflammatory effect of whole BV can be reproduced by two water-soluble fractions of BV (>20 kDa:BVAF1 and<10 kDa: BVAF3). Based on these scientific findings, BV and its effective water-soluble fractions have been proposed as potential anti-inflammatory and antinociceptive pharmaceuticals. While BV's anti-inflammatory and antinociceptive properties have been well documented, there have been no careful studies of potential, side effects of BV and its fractions when administered in the therapeutic range (BV, 5 microgram/kg; BVAF1, 0.2 microgram/kg: BVAF3, 3 microgram/kg; subcutaneous or intradermal). Such information is critical for future clinical use of BV in humans. Because of this paucity of information, the present study was designed to determine the general pharmacological/physiological effects of BV and its fractions administration on the rodent central nervous, cardiovascular, respiratory and gastrointestinal system. Subcutaneous BV and its fractions treatment did not produce any significant effects on general physiological functions at the highest dose tested (200-fold and 100-fold doses higher than that used clinically, respectively) except writhing test. These results demonstrate that doses of BV or BV subfractions in the therapeutic range or higher can be used as safe antinociceptive and anti-inflammatory agents.

Effects of BCG, lymphotoxin and bee venom on insulitis and development of IDDM in non-obese diabetic mice

To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.

Bioinsecticide action of the venom of africanized bees Apis mellifera Linnaeus 1758 (hymenoptera: apidae): I-the most susceptible age of diatrae saccharalis fabricius 1794 (Lepeletier: pyralidae) eggs to the venom action

The present paper aimed at testing the action of non-lyophilized venom of Africanized bees Apis mellifera through topical applications on Diatraea saccharalis egg masses. The CL50, DL50 and the most susceptible age of eggs to the venom topic application were also determined. Three-day-old eggs were the most susceptible to the venom action with CL50 equal to 8.6 mg/ml and DL50 equal to 0.173 mg/mass. The venom loses its action after being stored for 15 days.

Isolation, partial purification and pharmacodynamics of a slow contractile substance in the venom sac extract of the wasp Vespa cincta Fabr.

The venom of V. cincta contains acetylcholine (ACh), histamine and 5-hydroxytryptamine (5-HT). Blockers of these agonists did not block completely the hypotensive and smooth muscle contractile activity of venom. On smooth muscle, there was a residual slow contraction. The active substance which produced this slow contraction was separated by solvent extraction, gel filtration and TLC. The purified material (which has been provisionally designated "Vecikinin") lowered cat, rat and guinea pig blood pressure, increased amplitude of cardiac contraction, and increased capillary permeability. Vecikinin contracted several smooth muscle preparations (rat uterus, rat ascending colon, guinea pig ileum, guinea pig colon and rat ileum), while relaxing rat duodenum. Its contractile activity was not lost on boiling, but acid or alkali-boiling reduced its contractile activity. It was inactivated on incubation with chymotrypsin and carboxypeptidase but not with trypsin, pepsin or leucine aminopeptidase. It is a peptide, appears to be of low molecular weight, and could be distinguished from substance P, angiotensin, bradykinin and hornet or wasp kinin.