A novel chimeric protein with enhanced cytotoxic effects on breast cancer in vitro and in vivo. Issue 4 (30th November 2021)

• Record Type: Journal Article
• Authors: Hazrati, Fereshte; Saidijam, Massoud; Ahmadyousefi, Yaghoub; Nouri, Fatemeh; Ghadimipour, Hamidreza; Moradi, Mohammadreza; Haddadi, Rasool; Soleimani, Meysam
• Is Part Of: Proteins. Volume 90:Issue 4(2022)
• Page Start: 936
• Page End: 946
• Publication Date: 2021-11-30
• Subjects: apoptin -- breast cancer -- chimeric protein -- fusion protein -- p28 peptide; Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.26285
• Languages: English
• ISSNs: 0887-3585

Abstract

Abstract: In our previous study, we reported the design and recombinant production of the p28‐apoptin as a novel chimeric protein for breast cancer (BC) treatment. This study aimed to evaluate the inhibitory activity of the chimeric protein against BC cells in vitro and in vivo. We developed a novel multifunctional protein, consisting of p28, as a tumor‐homing killer peptide fused to apoptin as a tumor‐selective killer. The chimeric protein showed significantly higher toxicity in BC cell lines dose‐dependently than in non‐cancerous control cell lines. IC50 values were 1.41, 1.38, 6.13, and 264.49 μM for 4T1, MDA‐MB‐468, Vero, and HEK293 cells, respectively. The protein showed significantly enhanced uptake in 4T1 cancer cells compared with non‐cancerous Vero cells. We also showed that the p28‐apoptin chimeric protein binds significantly higher to human breast cancer tumor sections than the normal human breast tissue section. Also, significant apoptosis induction and tumor growth inhibition were observed in established tumor‐bearing mice accompanied by a decreased frequency of metastases. Our results support that the chimeric protein has inhibitory activity in vitro and in vivo, making it a promising choice in targeted cancer therapy.