Anticancer Activity of a Hexapeptide from Skate (Raja porosa) Cartilage Protein Hydrolysate in HeLa Cells.

Bin Wang,Yu-Qin Zhao,Chang-Feng Chi,Xin Pan,Fa-Yuan Hu

doi:10.3390/md14080153

Abstract

In this study, the hexapeptide Phe-Ile-Met-Gly-Pro-Tyr (FIMGPY), which has a molecular weight of 726.9 Da, was separated from skate (Raja porosa) cartilage protein hydrolysate using ultrafiltration and chromatographic methods, and its anticancer activity was evaluated in HeLa cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay indicated that FIMGPY exhibited high, dose-dependent anti-proliferation activities in HeLa cells with an IC50 of 4.81 mg/mL. Acridine orange/ethidium bromide (AO/EB) fluorescence staining and flow cytometry methods confirmed that FIMGPY could inhibit HeLa cell proliferation by inducing apoptosis. Western blot assay revealed that the Bax/Bcl-2 ratio and relative intensity of caspase-3 in HeLa cells treated with 7-mg/mL FIMGPY were 2.63 and 1.83, respectively, significantly higher than those of the blank control (p < 0.01). Thus, FIMGPY could induce apoptosis by upregulating the Bax/Bcl-2 ratio and caspase-3 activation. Using a DNA ladder method further confirmed that the anti-proliferation activity of FIMGPY was attributable to its role in inducing apoptosis. These results suggest that FIMGPY from skate cartilage protein hydrolysate may have applications as functional foods and nutraceuticals for the treatment and prevention of cancer.

Highlights

Cancer is one of the single most important causes of death in humans, inducing approximately 8.2 million deaths or 14.6% of all human deaths in 2012 [1]
Some peptides with anticancer and antioxidant activities have been purified from various protein hydrolysates [5]. (Leu-Ala-Asn-Ala-Lys) LANAK, which has a MW of 515.29 Da and is from oyster protein hydrolysates, was shown to initiate cancer cell death by inhibiting cancer cell growth, increasing DNA damage and apoptosis in the HT-29 colon cancer cell line, and displaying strong antioxidant potential as a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH)
The balance between proliferation and programmed cell death, which usually occurs via apoptosis, is maintained by regulating both processes to ensure the integrity of tissues and organs

Summary

Introduction

Cancer is one of the single most important causes of death in humans, inducing approximately 8.2 million deaths or 14.6% of all human deaths in 2012 [1]. Chemotherapy is the most common method used to eliminate cancer cells, prevent cancer recurrence, control cancer by slowing cell growth, and reduce symptoms [2]. Bioactive peptides, which consist of 2–20 amino acid residues, are inactive in the sequence of their parent proteins and can be released by enzymatic hydrolysis either during gastrointestinal digestion in the body or during food processing. Some peptides with anticancer and antioxidant activities have been purified from various protein hydrolysates [5]. (Leu-Ala-Asn-Ala-Lys) LANAK, which has a MW of 515.29 Da and is from oyster protein hydrolysates, was shown to initiate cancer cell death by inhibiting cancer cell growth, increasing DNA damage and apoptosis in the HT-29 colon cancer cell line, and displaying strong antioxidant potential as a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) Some peptides with anticancer and antioxidant activities have been purified from various protein hydrolysates [5]. (Leu-Ala-Asn-Ala-Lys) LANAK, which has a MW of 515.29 Da and is from oyster protein hydrolysates, was shown to initiate cancer cell death by inhibiting cancer cell growth, increasing DNA damage and apoptosis in the HT-29 colon cancer cell line, and displaying strong antioxidant potential as a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH)

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