The electrical shock method has been used to stimulate the bees to sting. The collector frame placed at the entrance of the hive and connected to a device which supplies electrical impulses, when bees receive a mild electric shock; they sting the surface of the collector sheet as they see this to be the source of danger. However, Honeybees didn t die after stinging the plate. The deposited venom between the glass and the protective material was dried then later scrapped off by a razor blade and collected in a dark bottle (Figure 1).

Bee venom powder (crude) of dose 1gm was dissolved in 1000 ml of sterile distilled water then filtered by 0.22 micron syring filter. That final concentration of the stock bee venom become 1 ug /ml (i.e. 1ul=1 ug), and kept at -20◦C. (1mg (dried BV) + 1ml (water) = Final concentration (1ug/1 ul)).

It was white crystalline powder, soluble in water. Concentrated solution was prepared in phosphate buffer solution (PBS).

Bee venom diluted solution 0.1 % was added to the oil in a ratio of 1 /10 (bee venom/ clove oil).

In the present case, Female patient (65 years old) observed inflamed and ulcerated birth mole that ignored for a while. Then after the huge abnormal growths it diagnosed as BCC followed by surgically removal (first surgical removal), but malignant growths recurrent during following year from first operation, then a second surgical removal of the recurrent BCC. A recurrence of cancer occurs 4 months later in the form of malignant growth in the skin of right ear, the lesion progress rapidly and invades the right ear (the beginning of the new intervention by bee venom).

The lesions extended laterally from previous sites; showings fingers channels through affected tissue, which appears blackish brown in color, under the grafted skin, it extends fingers in the deep tissue. Bee venom destruct these fingers with highly selective manner, as the drug only destroy the neoplastic growths, leaving healthy tissue with its normal blood capillaries. The gross picture of the lesions different in the course of treatment, the unapparent neoplastic growths was observed after removal of the destructed lesions, exhibiting the pathway of tumor cells spreading. Local injection was highly recommended, as it destroys abnormal cells and exposed the areas of the unapparent subcutaneous neoplastic lesions.

Performed by S/C injection of small dose of bee venom (0.1 ml) same as testing for penicillin and wait for at least one hour; however, no signs of allergy appeared. The patient was not hypersensitive to honeybees’ venom.

Figure, Figure 4, Figure 5, Figure 6, Figure 7.

Skin Basal Cell Carcinoma (SBCC) is a common malignancy affecting most probably populations with light skin. SBCC can cause significant local destructions depending on affected site. Biological transformation of BCC tends to occur at the base and edges of the growing neoplasm. The diagnosis of BCC can be suspected from clinical findings and confirmation of diagnosis requires histopathology of biopsy 123.

Apis mellifera L s venom (Honeybees) as injectable solutions (0.1%), have the potency to treat SBCC and stop the progress of this cancer. Bee venom is potent drug, with zero side effects in cases not hypersensitive against it. It cures the affected skin in very short time, without disfiguration of the patient body parts. Surgery was wrong choice in this case, giving more time for tumor cells to spread to the adjacent areas, leaving patients suffering another surgical intervention with permanent disfiguration of skin. Very small percentages of human have showed skin allergy from bee venom. However, Bee venom is safe drug when used in the recommended doses. Doses of bee venom which consider safe depends upon age, health conditions, type of illness, degree of affections, severity of illness, however in malignancy it is of special regime for every single case, depending on the practitioner experience and knowledge which should be of higher level 151617181920212223242526272829.

The signs of relief were after first injection, as the irritations and annoyance inside the ear shows instant relief and completely disappeared after only one week of bee venom therapy. The affected skin which was showing thickening and color changes become gradually smaller in size, with disappearance of the malignant growths picture from the affected area. Pus and exudates were accumulated after application of the topical ointment inside the ear, which removed and cleaned before each injection. The ear returned to normal status with comments of patient that she is hearing normally from the affected ear, feel signs of relief and health. These effects were seen after 10 days only from first bee venom application. The tumor area became smaller and smaller with color changes disappeared gradually (Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7).

For help in slowing local spreading of BCC, and avoiding accumulation of exudates inside the affected ear, the instructions were given for patient to sleep on the right side of body and putting the affected ear down during sleeping against the gravity. Complete rest is recommended. It is noted that after the injection of bee venom, the cancerous growths died and the exudates of dead cells were leaking from the affected skin. The strong effect of bee venom on these cancerous was specifically rapid and without any side effects.

Bee venom (Apis mellifera L) is safe and effective anticancer drug. As described by: Cassier et al., (1994) study the contribution of the sting sheaths of the worker to the defensive behavior of a bee colony. The structure of the proximal part of the sting sheath integument has all the characteristics of a primitive exocrine gland: porous cuticle with enlarged pore canals and epicuticular pores, and hypertrophied epithelial cells secreting an electron dense material. The non-volatile part of the secretory product embedded the setae of the sheaths. Individual recipient guards in the laboratory and as a group at hive entrances in a bee yard displayed defense behavior only when stimulated with either sting sheaths or with setaceous membrane, but not with any other gland or organ. Enhanced defensive reaction of guards has been observed when a venom gland or Koschewnikow's glands are added to either sting sheaths or to setaceous membrane. We demonstrate for the first time that the sting sheaths have the structure of an exocrine gland and that their secretions induce defensive behavior in guards 4.In agreement with: Moreau, (2012) who mentioned that many hymenopteran species, whatever their life style, have also evolved venom with properties which enable it to regulate microbial infections. Stinging Hymenoptera seems to constitute an under-exploited ecological niche for agents of vector-borne disease. Few parasitic or mutualistic microorganisms have been reported to be hosted by venom-producing organs or to be transmitted to stung animals. This may result from the presence of potent antimicrobial molecules in venoms, histological features of venom apparatuses and selective effects of venoms on immune defenses of targeted organisms 5.In accordance with: Islam et al., (2017) have mentioned that 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 6.

In accordance with: Xinjing Wang et al., (2017) have investigated the anti-cancer activity of melittin and its regulated mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by promoting cell apoptosis and cell-cycle arrest. Their study has indicated that melittin is capable of suppressing tumor growth and promoting gemcitabine sensitivity in PDAC by down regulating cholesterol pathway 7. In accordance with: Miran Jo et al., (2011) have 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 the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. They results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway 8. In accordance with: Jeong-Eun Huh et al., (2009) have mentioned that honeybees s venom significantly inhibited the viability of Lewis lung carcinoma (LLC) cells but did not affect peripheral blood mononuclear lymphocytes (PBML) cells. BV also inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). The western blotting analysis showed that BV inhibited AKT and MAPK phosphorylation in LLC cells and HUVECs and down regulated expression of VEGF and VEGFR-2 of LLC cells and HUVECs. They discover that Bee Venom effectively disrupted VEGF-induced neovascularization in Matrigel plugs in their in vivo angiogenesis assay. When given subcutaneously, Bee Venom was significantly suppressed tumor angiogenesis through inhibition of VEGF and VEGFR-2 in LLC model. Mice bearing subcutaneous LLC tumors were treated with 1 μg/ml or 10 μg/ml of Bee Venom, showing reductions ranging between 49% and 62% in primary tumor volume and reduction of spontaneous pulmonary metastasis occurrences. Furthermore, BV treatment in the spontaneous lung metastases model after primary tumor excision prolonged their median survival time from 27 to 58 days. These results suggest that the tumor-specific anti-angiogenic activity of Bee Venom takes effect during different stages of tumor progression by blocking the tyrosine phosphorylation of VEGFR-2, and validate the application of BV in lung cancer treatment 9. In accordance with: Son et al., (2007) have mentioned BV contains a variety of peptides, including melittin, apamin, adolapin, the mast-cell-degranulating (MCD) peptide, enzymes (i.e., phospholipase (PL) A (2), biologically active amines (i.e., histamine and epinephrine), and non-peptide components which have a variety of pharmaceutical properties 10. In accordance with: Oršolić, (2012) who mentioned that honeybee s venom has been used in the treatment of some immune-related diseases, as well as in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects 11.

However, the antimicrobial effects of bee venom are overwhelming. Socarras et al., (2017) have mentioned that Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use 12. In accordance with: Park et al., (2011) have mentioned that Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells (in vitro study). These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death (in vivo study). Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death 13.

In accordance with: Zheng et al., (2015) have mentioned that Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. They found that BV inhibited growth of colon cancer cells through induction of apoptosis, also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0-5 μg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. Besides, they found that BV blocked NF-κB activation by directly binding to NF-κB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF-κB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibition. BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti-proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-κB 14.

In the present case the origin of basal cell carcinoma was a birth mole on right side of head. A first sign of changes in skin mole was severe inflammation, treated with topical antibiotics, then with progress of lesions it diagnosed as classic BCC (rodent type), followed by the ineffective surgical removal. My findings are in accordance with Willis, 1960; who stated that untreated growths on the face may eventually destroy most of the facial soft tissues and bones or may penetrate to the skull or brain, and Elsewhere ¹⁹³⁰ write that I have reported penetration of the apex of the lung and of the spinal cord by a rodent cancer of the neck 30.