Abstract
BackgroundMelittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done.ResultsThis study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.ConclusionsOur study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.
Highlights
Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy
In the present in vitro and in vivo study, we aimed to study the delivery of melittin using niosomal formulations to increase its stability and controlled release to improve anticancer properties, induce apoptosis, inhibit migration and invasion, and effects on Bax, Bcl2, Caspase3, Caspase9, MMP2, and MMP9 mRNA expression in 4T1 and SKBR3 breast cancer cells and BALB/c tumor mice
The 64, and 128 μg/ml compared to control cell viability was decreased (P < 0.01**, and P < 0.001 ***) (Fig. 7c). These results indicated that melittin, and melittin-loaded niosome had more cytotoxicity effect on 4T1 cells, and as a model for breast mice mammary epithelial cancer cells compared to SKBR3 cell line after 72 h of treatment
Summary
A peptide component of honey bee venom, is an appealing candidate for cancer therapy. 40 BALB/c inbred mice were used; the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done These days breast cancer increased in the female population (Jemal et al 2011). If the tumor is high grade and node-positive, chemotherapy is generally practiced before targeted therapies depending on the hormonal/ErBb2 status of the tumor (Kontoyannis and Sweetland 2007). Anthracyclines, such as doxorubicin, epirubicin, and taxanes, are the current therapeutics for breast cancer treatment (Hernandez-Aya and Gonzalez-Angulo 2013). Fighting breast cancer still faces main obstacles, and finding new agents with the potential to be used in combination with current medicines to improve the therapeutic outcome and reduce the side effects is highly appreciated
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