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Research
Pejman Mortazavi
Department of Pathology, Faculty of Specialized Veterinary Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, Melittin and Melittin loaded niosome had been optimized and assessed the anticancer effect an 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 genes expression. 35 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.
Results: This 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 affect 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. Also enhanced the apoptosis rate and inhibitored 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 show a significant difference in Melittin loaded niosome and Melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.
Conclusions: Our 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 free form.
Keywords
Melittin, Nanoniosome, Breast cancer, Iimmunohistochemistry. renal and liver enzymes
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This is a preprint. It has not completed peer review.
Research
Pejman Mortazavi
Department of Pathology, Faculty of Specialized Veterinary Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 31 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nanoscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, Melittin and Melittin loaded niosome had been optimized and assessed the anticancer effect an 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 genes expression. 35 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.
Results: This 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 affect 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. Also enhanced the apoptosis rate and inhibitored 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 show a significant difference in Melittin loaded niosome and Melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.
Conclusions: Our 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 free form.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
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