Abstract
In this study, the anticancer effects of Porphyra haitanensis polysaccharides (PHPs) on human colon cancer cells and non-cancerous cells were evaluated. PHP was extracted by an ultrasonic/microwave-assisted method, and three fractions of polysaccharides (PHP-F1, PHP-F2 and PHP-F3) were obtained through a DEAE-52 cellulose ion-exchange column. The results of the cytotoxicity test showed that all of the PHP fractions had inhibitory effects on the growth of colon cancer cells HT-29, LoVo and SW-480, but no toxic effects on the normal human cells HaCaT. The fractions PHP-F2 and PHP-F3 had the most significant cytotoxicity on HT-29 cells. Studies on intracellular reactive oxygen species (ROS) levels, cell apoptosis, the apoptosis index (using Hoechst 33342 staining) and analysis of cell cycle arrest using flow cytometry revealed that the fractions PHP-F2 and PHP-F3 could apparently induce oxidative stress and apoptosis in HT-29 cells and cause cell G0–G1 phase arrest. These findings suggest that polysaccharides from P. haitanensis have anticancer effects on human colon cancer cells and therefore might be regarded as new candidates for the prevention and treatment of colon cancers.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arun A, Patel OPS, Saini D, Yadav PP, Konwar R (2017) Anti-colon cancer activity of Murraya koenigii leaves is due to constituent murrayazoline and O-methylmurrayamine A induced mTOR/AKT downregulation and mitochondrial apoptosis. Biomedicine & Pharmacotherapy 93:510–521. https://doi.org/10.1016/j.biopha.2017.06.065
Ashton JC (2015) Drug combination studies and their synergy quantification using the Chou-Talalay Method-Letter. Cancer Res 75(11):2400. https://doi.org/10.1158/0008-5472.Can-14-3763
Chen L, Huang GL (2018) Antitumor activity of polysaccharides: an overview. Curr Drug Targets 19(1):89–96. https://doi.org/10.2174/1389450118666170704143018
Chen Y-y, Xue Y-t (2019) Optimization of microwave assisted extraction, chemical characterization and antitumor activities of polysaccharides from Porphyra haitanensis. Carbohydr Polym 206:179–186. https://doi.org/10.1016/j.carbpol.2018.10.093
Chen CX, Nong ZH, Xie QQ, He JH, Cai WN, Tang XN, Chen XY, Huang RB, Gao Y (2017) 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice. Sci Rep. https://doi.org/10.1038/s41598-017-07162-3
Chen YJ, Jiang X, Xie HQ, Li XT, Shi LG (2018) Structural characterization and antitumor activity of a polysaccharide from ramulus mori. Carbohydr Polym 190:232–239. https://doi.org/10.1016/j.carbpol.2018.02.036
Chen XY, Li X, Zhang XB, You LJ, Cheung PCK, Huang RM, Xiao JB (2019a) Antihyperglycemic and antihyperlipidemic activities of a polysaccharide from Physalis pubescens L. in streptozotocin (STZ)-induced diabetic mice. Food Funct 10(8):4868–4876. https://doi.org/10.1039/c9fo00687g
Chen YA, Tang YP, Tang YH, Yang ZS, Ding GF (2019b) Serine protease from Nereis virens inhibits H1299 lung cancer cell proliferation via the PI3K/AKT/mTOR pathway. Marine Drugs. https://doi.org/10.3390/md17060366
Chen X, Zhang R, Li Y, Li X, You L, Kulikouskaya V, Hileuskaya K (2020) Degradation of polysaccharides from Sargassum fusiforme using UV/H2O2 and its effects on structural characteristics. Carbohydr Polym 230:115647. https://doi.org/10.1016/j.carbpol.2019.115647
Cheng Z, Song H, Yang Y, Liu Y, Liu Z, Hu H, Zhang Y (2015) Optimization of microwave-assisted enzymatic extraction of polysaccharides from the fruit of Schisandra chinensis Baill. Int J Biol Macromol 76:161–168. https://doi.org/10.1016/j.ijbiomac.2015.01.048
Cheong K-L, Qiu H-M, Du H, Liu Y, Khan BM (2018) Oligosaccharides derived from red seaweed: production, properties, and potential health and cosmetic applications. Molecules. https://doi.org/10.3390/molecules23102451
Dodgson KS, Price RG (1962) A note on the determination of the ester sulphate content of sulphated polysaccharides. Biochem J 84:106–110. https://doi.org/10.1042/bj0840106
DuBois M, Gilles KA, Hamilton JK, Rebers PA, Smith F (1956) Colorimetric method for determination of sugars and related substances. Anal Chem 28(3):350–356. https://doi.org/10.1021/ac60111a017
Filisetti-Cozzi TMCC, Carpita NC (1991) Measurement of uronic acids without interference from neutral sugars. Anal Biochem 197(1):157–162. https://doi.org/10.1016/0003-2697(91)90372-Z
Ghannam A, Murad H, Jazzara M, Odeh A, Allaf AW (2018) Isolation, Structural characterization, and antiproliferative activity of phycocolloids from the red seaweed Laurencia papillosa on MCF-7 human breast cancer cells. Int J Biol Macromol 108:916–926. https://doi.org/10.1016/j.ijbiomac.2017.11.001
Gong GP, Zhao JX, Wang CJ, Wei M, Dang TT, Deng YN, Sun J, Song S, Huang LJ, Wang ZF (2018) Structural characterization and antioxidant activities of the degradation products from Porphyra haitanensis polysaccharides. Process Biochem 74:185–193. https://doi.org/10.1016/j.procbio.2018.05.022
Han R, Pang D, Wen L, You L, Huang R, Kulikouskaya V (2019) In vitro digestibility and prebiotic activities of a sulfated polysaccharide from Gracilaria Lemaneiformis. J Funct Foods. https://doi.org/10.1016/j.jff.2019.103652
Huang S, Pang D, Li X, You L, Zhao Z, Cheung PC-K, Zhang M, Liu D (2019a) A sulfated polysaccharide from Gracilaria Lemaneiformis regulates cholesterol and bile acid metabolism in high-fat diet mice. Food Funct 10(6):3224–3236. https://doi.org/10.1039/c9fo00263d
Huang YM, Wang YF, Li WJ, Zhan JT, Lei JL, Li N, Tan LH, Qu C, Chen JN, Luo H (2019b) Evaluation of anti-fatigue property of Porphyridium cruentum in mice. Trop J Pharm Res 18(3):579–584. https://doi.org/10.4314/tjpr.v18i3.19
Khan BM, Qiu H-M, Xu S-Y, Liu Y, Cheong K-L (2020) Physicochemical characterization and antioxidant activity of sulphated polysaccharides derived from Porphyra haitanensis. Int J Biol Macromol 145:1155–1161. https://doi.org/10.1016/j.ijbiomac.2019.10.040
Liao BY, Zhu DY, Thakur K, Li L, Zhang JG, Wei ZJ (2017) Thermal and antioxidant properties of polysaccharides sequentially extracted from mulberry leaves (Morus alba L.). Molecules. https://doi.org/10.3390/molecules22122271
Liu G, Kuang S, Wu SM, Jin WH, Sun CM (2016) A novel polysaccharide from Sargassum integerrimum induces apoptosis in A549 cells and prevents angiogensis in vitro and in vivo. Sci Rep. https://doi.org/10.1038/srep26722
Liu QM, Xu SS, Li L, Pan TM, Shi CL, Liu H, Cao MJ, Su WJ, Liu GM (2017) In vitro and in vivo immunomodulatory activity of sulfated polysaccharide from Porphyra haitanensis. Carbohydr Polym 165:189–196. https://doi.org/10.1016/j.carbpol.2017.02.032
Liu A-J, Yu J, Ji H-Y, Zhang H-C, Zhang Y, Liu H-P (2018) Extraction of a novel cold-water-soluble polysaccharide from Astragalus membranaceus and Its antitumor and immunological activities. Molecules. https://doi.org/10.3390/molecules23010062
Liu B, Liu Q-M, Li G-L, Sun L-C, Gao Y-Y, Zhang Y-F, Liu H, Cao M-J, Liu G-M (2019) The anti-diarrhea activity of red algae-originated sulphated polysaccharides on ETEC-K88 infected mice. RSC Adv 9(5):2360–2370. https://doi.org/10.1039/c8ra09247h
Narayani SS, Saravanan S, Ravindran J, Ramasamy MS, Chitra J (2019) In vitro anticancer activity of fucoidan extracted from Sargassum cinereum against Caco-2 cells. Int J Biol Macromol 138:618–628. https://doi.org/10.1016/j.ijbiomac.2019.07.127
Qiu H-M, Veeraperumal S, Lv J-H, Wu T-C, Zhang Z-P, Zeng Q-K, Liu Y, Chen X-Q, Aweya JJ, Cheong K-L (2020) Physicochemical properties and potential beneficial effects of porphyran from Porphyra haitanensis on intestinal epithelial cells. Carbohydr Polym 246:116626. https://doi.org/10.1016/j.carbpol.2020.116626
Ren Y, Zheng G, You L, Wen L, Li C, Fu X, Zhou L (2017) Structural characterization and macrophage immunomodulatory activity of a polysaccharide isolated from Gracilaria lemaneiformis. J Funct Foods 33:286–296. https://doi.org/10.1016/j.jff.2017.03.062
Shi FL, Yan XL, Cheong KL, Liu Y (2018) Extraction, purification, and characterization of polysaccharides from marine algae Gracilaria lemaneiformis with anti-tumor activity. Process Biochem 73:197–203. https://doi.org/10.1016/j.procbio.2018.08.011
Sun NX, Liu HP, Liu SJ, Zhang XY, Chen P, Li WH, Xu XX, Tian WT (2018) Purification, preliminary structure and antitumor activity of exopolysaccharide produced by Streptococcus thermophilus CH9. Molecules. https://doi.org/10.3390/molecules23112898
Tan CP, Wu SH, Lai SS, Wang MX, Chen Y, Zhou LJ, Zhu YP, Lian W, Peng WL, Ji LN, Xu AL (2011) Synthesis, structures, cellular uptake and apoptosis-inducing properties of highly cytotoxic ruthenium-Norharman complexes. Dalton T 40(34):8611–8621. https://doi.org/10.1039/c1dt10084j
Vaikundamoorthy R, Krishnamoorthy V, Vilwanathan R, Rajendran R (2018) Structural characterization and anticancer activity (MCF7 and MDA-MB-231) of polysaccharides fractionated from brown seaweed Sargassum wightii. Int J Biol Macromol 111:1229–1237. https://doi.org/10.1016/j.ijbiomac.2018.01.125
Veeraperumal S, Qiu H-M, Zeng S-S, Yao W-Z, Wang B-P, Liu Y, Cheong K-L (2020) Polysaccharides from Gracilaria lemaneiformis promote the HaCaT keratinocytes wound healing by polarised and directional cell migration. Carbohydr Polym 241:116310. https://doi.org/10.1016/j.carbpol.2020.116310
Venkatraman KL, Mehta A (2019) Health benefits and pharmacological effects of Porphyra species. Plant Food Hum Nutr 74(1):10–17. https://doi.org/10.1007/s11130-018-0707-9
Wakiyama K, Kitajima Y, Tanaka T, Kaneki M, Yanagihara K, Aishima S, Nakamura J, Noshiro H (2017) Low-dose YC-1 combined with glucose and insulin selectively induces apoptosis in hypoxic gastric carcinoma cells by inhibiting anaerobic glycolysis. Sci Rep 7(1):12653. https://doi.org/10.1038/s41598-017-12929-9
Wali AF, Majid S, Rasool S, Shehada SB, Abdulkareem SK, Firdous A, Beigh S, Shakeel S, Mushtaq S, Akbar I, Madhkali H, Rehman MU (2019) Natural products against cancer: review on phytochemicals from marine sources in preventing cancer. Saudi Pharm J 27(6):767–777. https://doi.org/10.1016/j.jsps.2019.04.013
Wang Z, Wu B, Zhang X, Xu M, Chang H, Lu X, Ren X (2012) Purification of a polysaccharide from Boschniakia rossica and its synergistic antitumor effect combined with 5-Fluorouracil. Carbohydr Polym 89(1):31–35. https://doi.org/10.1016/j.carbpol.2012.02.024
Xie L, Shen M, Hong Y, Ye H, Huang L, Xie J (2020) Chemical modifications of polysaccharides and their anti-tumor activities. Carbohydr Polym 229:115436. https://doi.org/10.1016/j.carbpol.2019.115436
Xu Y, Zhu J, Zhou BR, Luo D (2012) Epigallocatechin-3-gallate decreases UVA-induced HPRT mutations in human skin fibroblasts accompanied by increased rates of senescence and apoptosis. Exp Ther Med 3(4):625–630. https://doi.org/10.3892/etm.2012.466
Xu SY, Huang XS, Cheong KL (2017a) Recent advances in marine algae polysaccharides: isolation, structure, and activities. Marine Drugs. https://doi.org/10.3390/md15120388
Xu T, Jin F, Wu KR, Ye ZP, Li N (2017b) Oridonin enhances in vitro anticancer effects of lentinan in SMMC-7721 human hepatoma cells through apoptotic genes. Exp Ther Med 14(5):5129–5134. https://doi.org/10.3892/etm.2017.5168
Xu SY, Liu JP, Huang XS, Du LP, Shi FL, Dong R, Huang XT, Zheng K, Liu Y, Cheong KL (2018) Ultrasonic-microwave assisted extraction, characterization and biological activity of pectin from jackfruit peel. LWT-Food Sci Technol 90:577–582. https://doi.org/10.1016/j.lwt.2018.01.007
Xu SY, Aweya JJ, Li N, Deng RY, Chen WY, Tang J, Cheong KL (2019) Microbial catabolism of Porphyra haitanensis polysaccharides by human gut microbiota. Food Chem 289:177–186. https://doi.org/10.1016/j.foodchem.2019.03.050
Xu SY, Chen XQ, Liu Y, Cheong KL (2020) Ultrasonic/microwave-assisted extraction, simulated digestion, and fermentation in vitro by human intestinal flora of polysaccharides from Porphyra haitanensis. Int J Biol Macromol 152:748–756. https://doi.org/10.1016/j.ijbiomac.2020.02.305
Yan J-K, Pei J-J, Ma H-L, Wang Z-B, Liu Y-S (2017) Advances in antitumor polysaccharides from phellinus sensu lato: production, isolation, structure, antitumor activity, and mechanisms. Crit Rev Food Sci Nutr 57(6):1256–1269. https://doi.org/10.1080/10408398.2014.984802
You LJ, Gong YF, Li LH, Hu X, Brennan C, Kulikouskaya V (2019) Beneficial effects of three brown seaweed polysaccharides on gut microbiota and their structural characteristics: an overview. Int J Food Sci Technol. https://doi.org/10.1111/ijfs.14408
Yu YY, Zhang YJ, Hu CB, Zou XY, Lin Y, Xia YY, You LJ (2019) Chemistry and immunostimulatory activity of a polysaccharide from Undaria pinnatifida. Food Chem Toxicol 128:119–128. https://doi.org/10.1016/j.fct.2019.03.042
Zhang X, Aweya JJ, Huang Z-X, Kang Z-Y, Bai Z-H, Li K-H, He X-T, Liu Y, Chen X-Q, Cheong K-L (2020a) In vitro fermentation of Gracilaria lemaneiformis sulfated polysaccharides and its agaro-oligosaccharides by human fecal inocula and its impact on microbiota. Carbohydr Polym 234:115894. https://doi.org/10.1016/j.carbpol.2020.115894
Zhang X, Liu Y, Chen X-Q, Aweya JJ, Cheong K-L (2020b) Catabolism of Saccharina japonica polysaccharides and oligosaccharides by human fecal microbiota. LWT 130:109635. https://doi.org/10.1016/j.lwt.2020.109635
Zheng L-X, Chen X-Q, Cheong K-L (2020) Current trends in marine algae polysaccharides: the digestive tract, microbial catabolism, and prebiotic potential. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2020.02.168
Zhou GZ, Shi YY, Cui LS, Li AF, Wang QQ, Liu M (2018) Oxymatrine induces A549 human non-small lung cancer cell apoptosis via extrinsic and intrinsic pathways. Mol Med Rep 17(1):1071–1076. https://doi.org/10.3892/mmr.2017.7982
Acknowledgements
This research was financially supported by grants from the National Natural Science Foundation of China (31901692); Natural Science Foundation of Guangdong Province, China (2018A030310151).
Author information
Authors and Affiliations
Contributions
KLC and XQC conceived and designed the experiments. WZY, SV and HMQ performed the experiment and wrote the manuscript. All authors revised the paper and contributed reagents/materials/analysis tools. All authors reviewed and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by the authors.
Rights and permissions
About this article
Cite this article
Yao, WZ., Veeraperumal, S., Qiu, HM. et al. Anti-cancer effects of Porphyra haitanensis polysaccharides on human colon cancer cells via cell cycle arrest and apoptosis without causing adverse effects in vitro. 3 Biotech 10, 386 (2020). https://doi.org/10.1007/s13205-020-02379-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13205-020-02379-y