Pleurotus eous polysaccharides suppress angiogenesis and induce apoptosis via ROS-dependent JNK activation and mitochondrial mediated mechanisms in MCF-7 human breast cancer cells

  • Jin-Kai Xu Department of General Surgery, The Second Affiliated Hospital of Xi?an Jiaotong University, Xi?an 710004
  • Qing-Gong Yuan Department of General Surgery, The Second Affiliated Hospital of Xi?an Jiaotong University, Xi?an 710004
  • Peng Luo Shanghai Topgen Biopharm Co., Ltd, Shanghai 200000
  • Xiao-Li Sun Department of General Surgery, The Second Affiliated Hospital of Xi?an Jiaotong University, Xi?an 710004
  • Jian-Cang Ma Department of General Surgery, The Second Affiliated Hospital of Xi?an Jiaotong University, Xi?an 710004
Keywords: Apoptosis, Angiogenesis, Breast cancer, Mushroom, Pleurotus eous, Polysaccharide


Breast cancer is one of the most prevalent cancers among women worldwide. Chemotherapy generally leads to drug resistance and severe side effects thus making it crucial to identify and develop highly efficient chemotherapeutic agents. Recently, edible mushrooms have been strongly investigated owing to their nutritional values and bioactive compounds with health benefits. The present study investigates the effects of polysaccharides isolated from the fruiting bodies of oyster mushroom, Pleutorus eous on MCF-7 human breast cancer cells. Viability of MCF-7 following exposure to P. eous polysaccharides (PEP) (50 - 250 µg/mL) were markedly decreased. A raise in the levels of Reactive Oxygen Species (ROS) and apoptotic cell counts were observed following PEP treatment. Futhermore, PEP down-regulated VEGF and Bcl-2 and raised caspase-3, caspase-9, Bax, phospho-JNK expressions and as well caused a significant decrease in mitochondrial membrane potential of MCF-7 cells. Thus, PEP effectively suppressed angiogenesis by down-regulating VEGF, and induced apoptosis.


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Bange J, Zwick E, Ullrich A. Molecular targets for breast cancer therapy and prevention. Nat Med. 2001; 7: 548-52.

Benhar M, Engelberg D, Levitzki A. ROS, stress-activated kinases and stresssignaling in cancer. EMBO Rep. 2002; 3: 420-25.

Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic toxicity: A systematic review of the evidence from randomized controlled trials. Int J Cancer 2008; 123: 1227-39.

Boon H, Stewart M, Kennard MA, Gray R, Sawka C, Brown JB, McWilliam C, Gavin A, Baron RA, Aaron D, Haines-Kamka T. Use of complementary/alternative medicine by breast cancer survivors in Ontario: Prevalence and perceptions. J Clin Oncol. 2000; 18: 2515-21.

Bradford MM. A rapid and sensitive method for the quantitation of micro-gram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-54.

Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003; 9: 653-60.

Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radical Bio Med. 2010; 48: 749-762.

Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000; 103: 239-52.

Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 2000; 10: 369-77.

Estaquier J, Vallette F, Vayssiere JL, Mignotte B. The mitochondrial pathways of apoptosis. Adv Exp Med Biol. 2012; 942: 157-83.

Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997; 89: 139-47.

Gasparini G, Toi M, Miceli R, Vermeulen PB, Dittadi R, Biganzoli E, Morabito A, Fanelli M, Gatti C, Suzuki H, Tominaga T, Dirix LY, Gion M. Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy. Cancer J Sci Am. 1999; 5: 101-11.

Han J, Goldstein LA, Gastman BR, Rabinowich H. Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. J Biol Chem. 2006; 281: 10153-63.

Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407: 770-76.

Hordegen P, Cabaret J, Hertzberg H, Langhans W, Maurer V. In vitro screening of six anthelmintic plant products against larval haemonchuscontortus with a modified methyl-thiazolyl-tetrazolium reduction assay. J Ethnopharmacol. 2006; 108: 85-89.

Hsu YL, Kuo PL, Lin LT, Lin CC. Asiatic acid, a triterpene, induces apoptosisand cell cycle arrest through activation of extracellular signal-regulated kinaseand p38 mitogen-activated protein kinase pathways in human breast cancer cells. J Pharmacol Exp Ther. 2005; 313: 333-44.

Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol. 1998; 10: 205-219.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancerstatistics. CA: Cancer J Clin. 2011; 61: 69-90.

Jose N, Janardhanan KK. Antioxidant and antitumour activity of Pleurotus florida. Curr Sci India 2001; 79: 941-43.

Kaufmann SH, Hengartner MO. Programmed cell death: Alive and well in the new millennium. Trends Cell Biol. 2001; 11: 526-34.

Ko HG, Park HG, Park SH, Choi CW, Kim SH, Park WM. Comparative study of mycelial growth and basidiomata formation in seven different species of the edible mushroom genus Hericium. Bioresource Technol. 2005; 96: 1439-44.

Lavi I, Friesem D, Geresh S, Hadar Y, Schwartz B. An aqueous polysaccharide extract from the edible mushroom Pleurotus ostreatus induces anti-proliferative and pro-apoptotic effects on HT-29 colon cancer cells. Cancer Lett. 2006; 244: 61-70.

Li X, Jiao LL, Zhang X, Tian WM, Chen S, Zhang LP. Anti-tumor and immunomodulating activities of proteoglycans from mycelium of Phellinus nigricans and culture medium. Int Immunopharmacol. 2008; 8: 909-15.

Li N, Li L, Fang JC, Wong JH, Ng TB, Jiang Y, Wang CR, Zhang NY, Wen TY, Qu LY, Lv PY, Zhao R, Shi B, Wang YP, Wang XY, Liu F. Isolation and identification of a novel polysaccharide-peptide complex with antioxidant, anti-proliferative and hypoglycaemic activities from the abalone mushroom. Bioscience Rep. 2012; 32: 221-28.

Lu HF, Sue CC, Yu CS, Chen SC, Chen GW, Chung JG. Diallyl disulfide(DADS) induced apoptosis undergo caspase-3 activity in human bladder cancerT24 cells. Food Chem Toxicol. 2004; 42: 1543-52 .

Manzi P, Gambelli L, Marconi S, Vivanti V, Pizzoferrato L. Nutrients in edible mushrooms: An inter-species comparative study. Food Chem. 1999; 65: 477-82.

Murthy KNC, Jayaprakasha GK, Kumar V, Rathore KS, Patil BS. Citrus limonin and its glucoside inhibit colon adenocarcinoma cell proliferation through apoptosis. J Agric Food Chem. 2011; 59: 2314-23.

Noori S, Hassan ZM. Tehranolide inhibits proliferation of MCF-7 human breast cancer cells by inducing G0/G1 arrest and apoptosis. Free Radical Biol Med. 2012; 52: 1987-99.

Pan JS, Hong MZ, Ren JL. Reactive oxygen species: A double-edged swordin oncogenesis. World J Gastroenterol. 2009; 15: 1702-07.

Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Update 2004; 7: 97-110.

Petrosillo G, Ruggiero FM, Paradies G. Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria. FASEB J. 2003; 17: 2202-08.

Rahman MA, Toi M. Anti-angiogenic therapy in breast cancer. Biomed Pharmacother. 2003; 57: 463-70.

Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signalling 2012; 24: 981-90.

Rogalska A, Koceva-Chy?a A, Jo´zwiak Z. Aclarubicin-induced ROS generation and collapse of mitochondrial membrane potential in human cancer cell lines. Chem Biol Interact. 2008; 176: 58-70.

Sarangi I, Ghosh D, Bhutia SK, Mallick SK, Maiti TK. Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int Immunopharmacol. 2006; 6: 1287-97.

Schneider BP, Miller KD. Angiogenesis of breast cancer. J Clin Oncol. 2005; 23: 1782-90.

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA: Cancer J Clin. 2012; 62: 220-41.

Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000; 5: 415-18.

Sinha K, Das J, Pal P, Sil P. Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013; 87: 1157-80.

Song KS, Li G, Kim JS, Jing K, Kim TD, Kim JP, Seo SB, Yoo JK, Park HD, Hwang BD, Lim K, Yoon WH. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/beta-catenin in SW480 human colon cancer cells. BMC Cancer 2011; 11: 307.

Stajic M, Vukojevic J, Duletic-Lausevic S. Biology of Pleurotus eryngii and role in biotechnological processes: A review. Crit Rev Biotechnol. 2009; 29: 55-66.

Stennicke HR, Salvesen GS. Properties of the caspases. Biochim Biophys Acta. 1998; 1387: 17-31

Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000; 279: L1005-28.

Wang YY, Khoo KH, Chen ST, Lin CC, Wong CH, Lin CH. Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides: Functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 2002; 10: 1057-62.

Wang JC, Hu SH, Liang ZC, Yeh CJ. Optimization for the production of water-soluble polysaccharide from Pleurotus citrinopileatus in submerged culture and its antitumor effect. Appl Microbiol Biotechnol. 2005; 67: 759-66.

Wang CR, Ng TB, Li L, Fang JC, Jiang Y, Wen TY, Qiao WT, Li N, Liu F. Isolation of a polysaccharide with antiproliferative, hypoglycemic, antioxidant and HIV-1 reverse transcriptase inhibitory activities from the fruiting bodies of the abalone mushroom Pleurotus abalonus. J Pharm Pharmacol. 2011; 63: 825-32.

Yang X, Lv Y, Tian L, Zhao Y. Composition and systemic immune activity of the polysaccharides from an herbal tea (Lycopus lucidus Turcz). J Agric Food Chem. 2010; 58: 6075-80.

Yoshiji H, Gomez D, Shibuya U. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 1996; 56: 2013-16.

Zhang Y, Chen F. Reactive oxygen species (ROS), trouble-makers between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK). Cancer Res. 2004; 64: 1902-05.

Zhang M, Cui SW, Cheung PCK, Wang Q. Antitumor polysaccharides from mushrooms: A review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci Tech. 2007; 18: 4-19.

Zhuang C, Mizuno T, Shimada A, Ito H, Suzuki C, Mayuzumi Y, Okamoto H, Ma Y, Li J. Antitumor protein-containing polysaccharides from a Chinese mushroom Fengweigu or Houbitake, Pleurotus sajor-caju (Fr.) sings. Biosci Biotech Biochem. 1993; 57: 901-06.

Zhuo L, Gong J, Yang R, Sheng Y, Zhou L, Kong X, Cao K. Inhibition of proliferation and differentiation and promotion of apoptosis by cyclin L2 in mouse embryonic carcinoma P19 cells. Biochem Biophys Res Commun. 2009; 18: 451-57.

How to Cite
Xu, J.-K., Q.-G. Yuan, P. Luo, X.-L. Sun, and J.-C. Ma. “Pleurotus Eous Polysaccharides Suppress Angiogenesis and Induce Apoptosis via ROS-Dependent JNK Activation and Mitochondrial Mediated Mechanisms in MCF-7 Human Breast Cancer Cells”. Bangladesh Journal of Pharmacology, Vol. 10, no. 1, Jan. 2015, pp. 78-86, doi:10.3329/bjp.v10i1.21153.
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