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On-line Access: 2019-01-07

Received: 2017-12-01

Revision Accepted: 2018-04-19

Crosschecked: 2018-12-05

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Tsun-Thai Chai


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Journal of Zhejiang University SCIENCE B

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Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum

Author(s):  Yixian Quah, Nor Ismaliza Mohd Ismail, Jillian Lean Sim Ooi, Yang Amri Affendi, Fazilah Abd Manan, Lai-Kuan Teh, Fai-Chu Wong, Tsun-Thai Chai

Affiliation(s):  Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, 31900 Kampar, Malaysia; more

Corresponding email(s):  chaitt@utar.edu.my

Key Words:  Anticancer therapy; Bioactive peptide; Cytotoxicity; HeLa cells; Sarcophyton glaucum; Soft coral

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Yixian Quah, Nor Ismaliza Mohd Ismail, Jillian Lean Sim Ooi, Yang Amri Affendi, Fazilah Abd Manan, Lai-Kuan Teh, Fai-Chu Wong, Tsun-Thai Chai. Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum[J]. Journal of Zhejiang University Science B, 2019, 20(7): 59-70.

@article{title="Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum",
author="Yixian Quah, Nor Ismaliza Mohd Ismail, Jillian Lean Sim Ooi, Yang Amri Affendi, Fazilah Abd Manan, Lai-Kuan Teh, Fai-Chu Wong, Tsun-Thai Chai",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum
%A Yixian Quah
%A Nor Ismaliza Mohd Ismail
%A Jillian Lean Sim Ooi
%A Yang Amri Affendi
%A Fazilah Abd Manan
%A Lai-Kuan Teh
%A Fai-Chu Wong
%A Tsun-Thai Chai
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 1
%P 59-70
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer

T1 - Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum
A1 - Yixian Quah
A1 - Nor Ismaliza Mohd Ismail
A1 - Jillian Lean Sim Ooi
A1 - Yang Amri Affendi
A1 - Fazilah Abd Manan
A1 - Lai-Kuan Teh
A1 - Fai-Chu Wong
A1 - Tsun-Thai Chai
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 1
SP - 59
EP - 70
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -

Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.

软珊瑚Sarcophyton glaucum中新型细胞毒性寡肽的纯化与鉴定

目的:纯化和鉴定软珊瑚Sarcophyton glaucum蛋白水解物中的细胞毒性肽.
创新点:首次从软珊瑚S. glaucum中发现具有癌细胞毒性的寡肽,开发了一种有潜力的新型抗癌药物.
方法:通过碱性蛋白酶、胰凝乳蛋白酶、木瓜蛋白酶和胰蛋白酶产生软珊瑚S. glaucum蛋白质水解物,并通过MTT法评估其对人宫颈癌HeLa细胞的毒性.通过膜超滤、凝胶过滤色谱、固相萃取和反相高效液相色谱等技术进一步提纯肽;采用从头测序法(de novo sequencing)进行肽鉴定;根据所鉴定的序列,进一步确定合成肽的细胞毒性.
结论:从软珊瑚S. glaucum的木瓜蛋白酶水解物中鉴定出三种新型肽序列:AGAPGG、AERQ和RDTQ(分子量分别为428.45、502.53和518.53 Da).此三种寡肽具有对HeLa的细胞毒性,其半最大效应浓度(EC50)值各为8.6、4.9和5.6 mmol/L,为抗癌药物5-氟尿嘧啶的3.3、5.8和5.1倍.当测试对非癌细胞Hek293的毒性时,这三种肽仅显示16%、25%和11%的细胞毒性.因此,AERQ、AGAPGG和RDTQ有很大的潜力成为肽类抗癌药物.

关键词组:抗癌治疗;活性肽;细胞毒性;HeLa细胞;Sarcophyton glaucum;软珊瑚

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abdel-Lateff A, Alarif WM, Ayyad SEN, et al., 2015. New cytotoxic isoprenoid derivatives from the Red Sea soft coral Sarcophyton glaucum. Nat Prod Res, 29(1):24-30.

[2]Al-Lihaibi SS, Alarif WM, Abdel-Lateff A, et al., 2014. Three new cembranoid-type diterpenes from Red Sea soft coral Sarcophyton glaucum: isolation and antiproliferative activity against HepG2 cells. Eur J Med Chem, 81:314-322.

[3]Bradford MM, 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72(1-2):248-254.

[4]Chai TT, Law YC, Wong FC, et al., 2017. Enzyme-assisted discovery of antioxidant peptides from edible marine invertebrates: a review. Mar Drugs, 15(2):42.

[5]Chao CH, Li WL, Huang CY, et al., 2017. Isoprenoids from the soft coral Sarcophyton glaucum. Mar Drugs, 15(7):202.

[6]Chen LL, Song LY, Li TF, et al., 2013. A new antiproliferative and antioxidant peptide isolated from Arca subcrenata. Mar Drugs, 11(6):1800-1814.

[7]Chen YC, Chang HS, Wang CT, et al., 2009. Antioxidative activities of hydrolysates from duck egg white using enzymatic hydrolysis. Asian Austral J Anim Sci, 22(11):1587-1593.

[8]Cordeiro, R., van Ofwegen, L., Williams, G., 2010. World List of Octocorallia. Sarcophyton glaucum (Quoy & Gaimard, 1833). http://www.marinespecies.org/aphia.php?p=taxdetails&id=209621 [Accessed on Sept. 25, 2017].

[9]Daliri EBM, Oh DH, Lee BH, 2017. Bioactive peptides. Foods, 6(5):32.

[10]de Lumen BO, 2005. Lunasin: a cancer-preventive soy peptide. Nutr Rev, 63(1):16-21.

[11]Dennison SR, Whittaker M, Harris F, et al., 2006. Anticancer α-helical peptides and structure/function relationships underpinning their interactions with tumour cell membranes. Curr Protein Pept Sci, 7(6):487-499.

[12]Fabricius KE, Alderslade P, 2001. Soft Corals and Sea Fans: A Comprehensive Guide to the Tropical Shallow Water Genera of the Central-West Pacific, the Indian Ocean and the Red Sea. Australian Institute of Marine Science, Townsville, Australia, p.264.

[13]Fahmy H, Zjawiony JK, Konoshima T, et al., 2006. Potent skin cancer chemopreventing activity of some novel semi-synthetic cembranoids from marine sources. Mar Drugs, 4(2):28-36.

[14]Fan XD, Bai L, Mao XL, et al., 2017. Novel peptides with anti-proliferation activity from the Porphyra haitanesis hydrolysate. Process Biochem, 60:97-107.

[15]Ferlay J, Soerjomataram I, Ervik M, et al., 2018. GLOBOCAN 2018, Cancer tomorrow: estimated number of incident cases from 2018 to 2040, all cancers, both sexes, all ages. International Agency for Research on Cancer, Lyon, France. http://gco.iarc.fr/tomorrow/graphic-line?type=0&population=900&mode=population&sex=0&cancer=39&age_group=value&apc_male=0&apc_female=0 [Accessed on Dec. 20, 2018].

[16]Gabernet G, Müller AT, Hiss JA, et al., 2016. Membranolytic anticancer peptides. Med Chem Commun, 7(12):2232-2245.

[17]He GQ, Xuan GD, Ruan H, et al., 2005. Optimization of angiotensin I-converting enzyme (ACE) inhibition by rice dregs hydrolysates using response surface methodology. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 6(6):508-513.

[18]Hegazy ME, El-Beih AA, Moustafa AY, et al., 2011. Cytotoxic cembranoids from the Red Sea soft coral Sarcophyton glaucum. Nat Prod Commun, 6(12):1809-1812.

[19]Hsu KC, Li-Chan ECY, Jao CL, 2011. Antiproliferative activity of peptides prepared from enzymatic hydrolysates of tuna dark muscle on human breast cancer cell line MCF-7. Food Chem, 126(2):617-622.

[20]Huang CY, Sung PJ, Uvarani C, et al., 2015. Glaucumolides A and B, biscembranoids with new structural type from a cultured soft coral Sarcophyton glaucum. Sci Rep, 5:15624.

[21]Huang YB, Wang XF, Wang HY, et al., 2011. Studies on mechanism of action of anticancer peptides by modulation of hydrophobicity within a defined structural framework. Mol Cancer Ther, 10(3):416-426.

[22]Hung CC, Yang YH, Kuo PF, et al., 2014. Protein hydrolysates from tuna cooking juice inhibit cell growth and induce apoptosis of human breast cancer cell line MCF-7. J Funct Foods, 11:563-570.

[23]Jumeri, Kim SM, 2011. Antioxidant and anticancer activities of enzymatic hydrolysates of solitary tunicate (Styela clava). Food Sci Biotechnol, 20(4):1075-1085.

[24]Kim EK, Kim YS, Hwang JW, et al., 2013. Purification and characterization of a novel anticancer peptide derived from Ruditapes philippinarum. Process Biochem, 48(7):1086-1090.

[25]Li Y, Yu JM, 2015. Research progress in structure-activity relationship of bioactive peptides. J Med Food, 18(2):147-156.

[26]Minkiewicz P, Dziuba J, Iwaniak A, et al., 2008. BIOPEP database and other programs for processing bioactive peptide sequences. J AOAC Int, 91(4):965-980.

[27]Ngo DH, Vo TS, Ngo DN, et al., 2012. Biological activities and potential health benefits of bioactive peptides derived from marine organisms. Int J Biol Macromol, 51(4):378-383.

[28]Nielsen PM, Petersen D, Dambmann C, 2001. Improved method for determining food protein degree of hydrolysis. J Food Sci, 66(5):642-646.

[29]Nurdiani R, Vasiljevic T, Yeager T, et al., 2017. Bioactive peptides with radical scavenging and cancer cell cytotoxic activities derived from Flathead (Platycephalus fuscus) by-products. Eur Food Res Technol, 243(4):627-637.

[30]Pan X, Zhao YQ, Hu FY, et al., 2016. Anticancer activity of a hexapeptide from skate (Raja porosa) cartilage protein hydrolysate in HeLa cells. Mar Drugs, 14(8):153.

[31]Pangestuti R, Kim SK, 2017. Bioactive peptide of marine origin for the prevention and treatment of non-communicable diseases. Mar Drugs, 15(3):67.

[32]Picot L, Bordenave S, Didelot S, et al., 2006. Antiproliferative activity of fish protein hydrolysates on human breast cancer cell lines. Process Biochem, 41(5):1217-1222.

[33]Qian ZJ, Je JY, Kim SK., 2007. Antihypertensive effect of angiotensin I converting enzyme-inhibitory peptide from hydrolysates of bigeye tuna dark muscle, Thunnus obesus. J Agric Food Chem, 55(21):8398-8403.

[34]Quah Y, Ismail NIM, Ooi JLS, et al., 2017. Identification of novel cytotoxic peptide KENPVLSLVNGMF from marine sponge Xestospongia testudinaria, with characterization of stability in human serum. Int J Pept Res Ther, 24(1):189-199.

[35]Schmidt N, Mishra A, Lai GH, et al., 2010. Arginine-rich cell-penetrating peptides. FEBS Lett, 584(9):1806-1813.

[36]Shan YP, Huang JF, Tan JJ, et al., 2012. The study of single anticancer peptides interacting with HeLa cell membranes by single molecule force spectroscopy. Nanoscale, 4(4):1283-1286.

[37]Simmons TL, Andrianasolo E, McPhail K, et al., 2005. Marine natural products as anticancer drugs. Mol Cancer Ther, 4(2):333-342.

[38]Song R, Wei RB, Luo HY, et al., 2014. Isolation and identification of an antiproliferative peptide derived from heated products of peptic hydrolysates of half-fin anchovy (Setipinna taty). J Funct Foods, 10:104-111.

[39]Sutradhar KB, Amin ML, 2014. Nanotechnology in cancer drug delivery and selective targeting. Int Sch Res Notices, 2014:939378.

[40]Tada N, Horibe T, Haramoto M, et al., 2011. A single replacement of histidine to arginine in EGFR-lytic hybrid peptide demonstrates the improved anticancer activity. Biochem Biophys Res Commun, 407(2):383-388.

[41]Wang B, Li L, Chi CF, et al., 2013. Purification and characterisation of a novel antioxidant peptide derived from blue mussel (Mytilus edulis) protein hydrolysate. Food Chem, 138(2-3):1713-1719.

[42]Wang YK, He HL, Wang GF, et al., 2010. Oyster (Crassostrea gigas) hydrolysates produced on a plant scale have antitumor activity and immunostimulating effects in BALB/c mice. Mar Drugs, 8(2):255-268.

[43]Wang ZJ, Zhang XW, 2016. Inhibitory effects of small molecular peptides from Spirulina (Arthrospira) platensis on cancer cell growth. Food Funct, 7(2):781-788.

[44]You LJ, Zhao MM, Liu RH, et al., 2011. Antioxidant and antiproliferative activities of loach (Misgurnus anguillicaudatus) peptides prepared by papain digestion. J Agric Food Chem, 59(14):7948-7953.

[45]Zheng LH, Lin XK, Wu N, et al., 2013. Targeting cellular apoptotic pathway with peptides from marine organisms. Biochim Biophys Acta, 1836(1):42-48.

[46]List of electronic supplementary materials

[47]Fig. S1 A representative SPE elution prolife of GF3

[48]Fig. S2 Peptide content of SPE fractions

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