Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by amygdaline-ZHER2 affibody conjugate

• Published in: Molecular biology reports Vol. 47; no. 9; pp. 7139 - 7151
• Main Authors: Moradipoodeh, Bahman, Jamalan, Mostafa, Zeinali, Majid, Fereidoonnezhad, Masood, Mohammadzadeh, Ghorban
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.09.2020; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Apoptosis; Bax protein; Bcl-2 protein; Biomedical and Life Sciences; Breast cancer; Breast carcinoma; Cell death; Cytotoxicity; ErbB-2 protein; Histology; Life Sciences; Morphology; Original Article; Tumor cell lines; SK-BR-3 cell; Amygdalin-Z; Breast cancer; Z; affibody; Human epidermal receptor-2; Amygdalin; MCF-7 cell; affibody conjugate
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-05782-z

Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the amygdalin-Z HER2 affibody conjugate on two breast carcinoma cell lines. The Z HER2 affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z HER2 affibody was conjugated to amygdalin. The cytotoxic effects of amygdalin and its Z HER2 affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC 50  = 14.2 mg ml −1 ) and SK-BR-3 cells (IC 50  = 13.7 mg ml −1 ). However, the amygdalin-Z HER2 affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC 50  = 8.27 mg ml −1 ) than MCF-7 cells (IC 50  = 19.8 mg ml −1 ). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the amygdalin-Z HER2 affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed amygdalin-Z HER2 affibody conjugate.