| Summary: | Protein hydrolysates from various sources, including tuna cooking juice, soy protein isolate, sodium caseinate, wheat gluten and skin gelatin from porcine, tilapia, halibut and milkfish were analyzed to screen their antiproliferative activities against the human oral squamous carcinoma cell line, HSC-3. The soy protein isolate was selected for further investigations based on its hydrolysates with bromelain (SB) and thermolysin (ST), showing the greatest inhibition of cell growth. The SB and ST hydrolysates showed antiproliferative activities up to 35.45–76.39% against HSC-3 cells at 72 h, and their IC<sub>50</sub> values were 0.74 and 0.60 mg/mL, respectively. SB and ST induced cell cycle arrest in the S phase through a pathway independent of p21 and p27 protein expression. Further, ST induced the apoptosis of HSC-3 cells by downregulating expression of Bcl-2, PARP, caspase 3 and caspase 9, but an upregulating expression of p53 and cleaved caspase 3. Unlike ST, SB may induce necrosis on HSC-3 cells. Thus, soybean hydrolysates may be a good source for providing antiproliferative peptides against HSC-3, while SB and ST may have the potential to be developed as functional foods.
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