Preparation of Immunotoxin Herceptin-Botulinum and Killing Effects on Two Breast Cancer Cell Lines

Hajighasemlou, Saieh; Alebouyeh, Mahmoud; Rastegar, Hossein; Manzari, Mojgan Taghizadeh; Mirmoghtadaei, Milad; Moayedi, Behjat; Ahmadzadeh, Maryam; Parvizpour, Farzad; Johari, Behrooz; Naeini, Maria Moslemi; Farajollahi, Mohammad M

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저자정보: Hajighasemlou, Saieh (Iran Food and Drug Administration) Alebouyeh, Mahmoud (Iran Food and Drug Administration) Rastegar, Hossein (Iran Food and Drug Administration) Manzari, Mojgan Taghizadeh (Iran Food and Drug Administration) Mirmoghtadaei, Milad (Tehran University of Medical Sciences, International Campus [TUMS-IC]) Moayedi, Behjat (Isfahan University of Medical Sciences) Ahmadzadeh, Maryam (Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences) Parvizpour, Farzad (Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences) Johari, Behrooz (Department of Biotechnology, Pasteur Institute of Iran) Naeini, Maria Moslemi (Cellular & Molecular Research Centre, Iran University of Medical Sciences) Farajollahi, Mohammad M (Cellular & Molecular Research Centre, Iran University of Medical Sciences)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제14호

발행연도: 2015.1

수록면: 5,977 - 5,981 (5page)

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Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.

#Breast cancer #herceptin #botulinum toxin #HER2 #SK-BR-3 #BT-474

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