Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 17 5 2018 10 14 436 452 EN Sogol Shahidi Department of Marine Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran Shahla Jamili Department of Marine Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran Pargol Ghavam Mostafavi Department of Marine Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran Sassan Rezaie Division of Molecular Biology, Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mohammadreza Khorramizadeh Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran 2017 08 21 2017 09 05 Marine novel natural products have been applied for cancer therapy. Enzyme-digested gelatin hydrolysates have proven to serve as promising sources of potent biologically active peptides. Potential anti-breast cancer properties of the extracted Ficin-digesterd gelatin hydrolysate from Indian squid (Uroteuthis duvauceli) was extensively characterized by cellular and animal models. Gelatin was extracted from squid skin, hydrolyzed by Ficin, and characterized by standard physico-chemical methods. Ficin-digested gelatin hydrolysate was used at various doses of 0-0.1 mg/mL for assessment of MCF-7 and MDA-MB-231 breast cancer cells versus HUVEC normal cells. Cytotoxicity, phase-contrast morphological examination, apoptosis/necrosis, clonal-growth, cell-migration, Matrix-metalloproteinases (MMPs) zymography, and Western blotting were used for cellular assessments. For animal studies, breast tumor-induced BALB/c mice received hydrolyzed gelatin regimen, followed by tumor size/growth and immune-histochemical analyses. Significant inhibition of MCF-7 and MDA-MB-231 with no cytotoxicity on HUVEC cells were detected. Apoptosis was increased in cancer cells, as revealed by elevated ratio of cleaved caspase-3 and PARP. MMP-2 and MMP-9 activities in both cancer cells were diminished. In mice, gelatin hydrolysate prevented weight loss, decreased tumor size, induced p53, and down-regulated Ki67 levels. These findings suggest that Ficin-digested gelatin hydrolysate could be a beneficial candidate for novel breast cancer therapies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1635 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1635/1362