<em>Agaricus blazei</em> extract (FA‑2‑b‑&beta;) induces apoptosis in chronic myeloid leukemia cells

Sun,Yanqing; Cheng,Mingxia; Dong,Li; Yang,Kehu; Ma,Zhiyuan; Yu,Shangrui; Yan,Peijing; Bai,Kuntian; Zhu,Xiaolong; Zhang,Qike

doi:10.3892/ol.2020.12133

Agaricus blazei extract (FA‑2‑b‑β) induces apoptosis in chronic myeloid leukemia cells

Authors:
- Yanqing Sun
- Mingxia Cheng
- Li Dong
- Kehu Yang
- Zhiyuan Ma
- Shangrui Yu
- Peijing Yan
- Kuntian Bai
- Xiaolong Zhu
- Qike Zhang
View Affiliations

Affiliations: Department of Hematology, Gansu Provincial Hospital, Lanzhou, Gansu 730000, P.R. China, Department of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China, Evidence‑Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Institute of Clinical Research and Evidence Based Medicine, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Published online on: September 21, 2020 https://doi.org/10.3892/ol.2020.12133
Article Number: 270
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Agaricus blazei Murill (AbM) is a mushroom belonging to the Basidiomycetes family, which is believed to have antitumor and antioxidative activities. Proteoglycans and ergosterol are considered the key compounds of AbM for antitumor properties and so are used in complementary and alternative medicine as an anticancer drug. AbM is used to avoid serious side effects that would inevitably affect patients. Currently, the efficacy of AbM against chronic myeloid leukemia (CML) has not been established. The present study aimed to investigate the antitumor activities of the acidic RNA protein complex, FA‑2‑b‑β, extracted from wild edible AbM. The CML K562 cells or primary CML bone marrow (BM) cells were treated with FA‑2‑b‑β at different concentrations and time points. CML cell line proliferation and apoptosis were determined using the CCK‑8 assay or Annexin V/propidium iodide (PI) labeling, RT‑qPCR and western blotting was performed to determine the involvement of the Wnt/β‑catenin‑associated apoptotic pathway. The results of the present study demonstrated that FA‑2‑b‑β has a high anti‑proliferative potency and strong pro‑apoptotic effects. Thus, daily intake of mushrooms containing FA‑2‑b‑β may be an adequate source as an alternative medicine in the management of CML, and may provide useful information for the development of a novel therapeutic target in this area.

View Figures

View References

1	Bamodu OA, Kuo KT, Yuanc LP, et al: HDAC inhibitor suppresses proliferation and tumorigenicity of drug-resistant chronic myeloid leukemia stem cells through regulation of hsa-miR-196a targeting BCR/ABL1. Exp Cell Res. 370:519–530. 2018. View Article : Google Scholar : PubMed/NCBI
2	Zhou H, Mak PY, Mu H, Mak DH, Zeng Z, Cortes J, Liu Q, Andreeff M and Carter BZ: Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 31:2065–2074. 2017. View Article : Google Scholar : PubMed/NCBI
3	Xiao X, Liu P, Li D, Xia Z, Wang P, Zhang X, Liu M, Liao L, Jiao B and Ren R: Combination therapy of BCR-ABL-positive B cell acute lymphoblastic leukemia by tyrosine kinase inhibitor dasatinib and c-JUN N-terminal kinase inhibition. J Hematol Oncol. 13:802020. View Article : Google Scholar : PubMed/NCBI
4	Deshpande A and Buske C: Knocking the Wnt out of the sails of leukemia stem cell development. Cell Stem Cell. 1:597–598. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zovko A, Yektaei-Karin E, Daniel S, Nilsson A, Wallvik J and Stenke L: Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis. Oncol Rep. 40:902–908. 2018.PubMed/NCBI
6	Braun TP, Eide CA and Druker BJ: Response and resistance to BCR-ABL1-targeted therapies. Cancer Cell. 37:530–542. 2020. View Article : Google Scholar : PubMed/NCBI
7	Vetrie D, Helgason GV and Copland M: The leukaemia stem cell: Similarities, differences and clinical prospects in CML and AML. Nat Rev Cancer. 20:158–173. 2020. View Article : Google Scholar : PubMed/NCBI
8	Kumar R, Pereira RS, Zanetti C, et al: Specific, targetable interactions with the microenvironment influence imatinib-resistant chronic myeloid leukemia. Leukemia. 34:2087–2101. 2020. View Article : Google Scholar : PubMed/NCBI
9	Cronan TA, Kaplan RM, Posner L, Blumberg E and Kozin F: Prevalence of the use of unconventional remedies for arthritis in a metropolitan community. Arthritis Rheum. 32:1604–1607. 1989. View Article : Google Scholar : PubMed/NCBI
10	AlGhamdi KM, Khurrum H, Al-Natour SH, et al: Use of complementary and alternative medicine among dermatology outpatients: Results from a national survey. J Cutan Med Surg. 19:570–579. 2015. View Article : Google Scholar : PubMed/NCBI
11	Wu L, Yu J, Chen R, Liu Y, Lou L, Wu Y, Huang L, Fan Y, Gao P, Huang M, et al: Dual inhibition of Bcr-Abl and Hsp90 by C086 potently inhibits the proliferation of imatinib-resistant CML cells. Clin Cancer Res. 21:833–843. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ryan NM, Vertigan AE and Birring SS: An update and systematic review on drug therapies for the treatment of refractory chronic cough. Expert Opin Pharmacother. 19:687–711. 2018. View Article : Google Scholar : PubMed/NCBI
13	Tsai WJ, Yang SC, Huang YL, Chen CC, Chuang KA and Kuo YC: 4-Hydroxy-17-methylincisterol from Agaricus blazei decreased cytokine production and cell proliferation in human peripheral blood mononuclear cells via inhibition of NF-AT and NF-κB activation. Evid Based Complement Alternat Med. 2013:4359162013. View Article : Google Scholar : PubMed/NCBI
14	Hetland G, Tangen JM, Mahmood F, et al: Antitumor, anti-inflammatory and antiallergic effects of Agaricus blazei mushroom Extract and the related medicinal Basidiomycetes mushrooms, Hericium erinaceus and Grifola frondosa: A review of preclinical and clinical studies. Nutrients. 12:13392020. View Article : Google Scholar
15	Li Y, Sheng Y, Lu X, Guo X, Xu G, Han X, An L and Du P: Isolation and purification of acidic polysaccharides from Agaricus blazei Murill and evaluation of their lipid-lowering mechanism. Int J Biol Macromol. 157:276–287. 2020. View Article : Google Scholar : PubMed/NCBI
16	Sun YQ, Guo TK, Xi YM, Chen C, Wang J and Wang ZR: Effects of AZT and RNA-protein complex (FA-2-b-β) extracted from Liang Jin mushroom on apoptosis of gastric cancer cells. World J Gastroenterol. 13:4185–4191. 2007. View Article : Google Scholar : PubMed/NCBI
17	Lin MH, Lee KM, Hsu CY, et al: Immunopathological effects of Agaricus blazei Murill polysaccharides against Schistosoma mansoni infection by Th1 and NK1 cells differentiation. Int Immunopharmacol. 73:502–514. 2019. View Article : Google Scholar : PubMed/NCBI
18	Ziliotto L, Pinheiro F, Barbisan LF and Rodrigues MAM: Screening for in vitro and in vivo antitumor activities of the mushroom Agaricus Blazei. Nutr Cancer. 61:245–250. 2009. View Article : Google Scholar : PubMed/NCBI
19	Pak S, Park S, Kim Y, et al: Correction to: The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway. J Exp Clin Cancer Res. 38:4402019. View Article : Google Scholar : PubMed/NCBI
20	Lin HJ, Huang Y, Huang WL, Feng XL, Peng Y, Zhang XJ, Jin Z and Fan XM: Regulatory mechanism of microRNA and Wnt/β-catenin signaling pathway in tumorigenesis and metastasis. Sci Sin. 45:5–14. 2018.
21	Li ZJ, Qiu LG, Li X, et al: Expression of β-catenin gene in CML and its relationship with bcr/abl. J Exp Hematol. 15:931–935. 2007.(In Chinese).
22	Hu Y, Yu K, Wang G, Zhang D, Shi C, Ding Y, Hong D, Zhang D, He H, Sun L, et al: Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell. Biochem Pharmacol. 150:280–292. 2018. View Article : Google Scholar : PubMed/NCBI
23	Mizuno T, Inagaki R, Kanao T, Hagiwara T, Nakamura T, Ito H, Shimura K, Sumiya T and Asakura A: Antitumor activity and some properties of water-insoluble hetero-glycans from ‘Himematsutake’, the fruiting body of Agaricus blazei Murill. Agr Biol Chem. 54:2897–2905. 1990. View Article : Google Scholar
24	Dong S, Furutani Y, Suto Y, Furutani M, Zhu Y, Yoneyama M, Kato T, Itabe H, Nishikawa T, Tomimatsu H, et al: Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract. Microbiol Res. 167:231–237. 2012. View Article : Google Scholar : PubMed/NCBI
25	He B, Wang Q, Liu X, et al: A novel HDAC inhibitor chidamide combined with imatinib synergistically targets tyrosine kinase inhibitor resistant chronic myeloid leukemia cells. Biomed Pharmacother. 129:1103902020. View Article : Google Scholar : PubMed/NCBI
26	Tang K and Lightner DV: Detection and quantification of infectious hypodermal and hematopoietic necrosis virus in penaeid shrimp by real-time PCR. Dis Aquat Organ. 44:79–85. 2001. View Article : Google Scholar : PubMed/NCBI
27	Chen SH, Hsieh YY, Tzeng HE, et al: ABL genomic editing sufficiently abolishes oncogenesis of human chronic myeloid leukemia cells in vitro and in vivo. Cancers (Basel). 12:13992020. View Article : Google Scholar
28	Ryu H, Nam KY, Kim JS, Hwang SG, Song JY and Ahn J: The small molecule AU14022 promotes colorectal cancer cell death via p53-mediated G2/M-phase arrest and mitochondria-mediated apoptosis. J Cell Physiol. 233:4666–4676. 2018. View Article : Google Scholar : PubMed/NCBI
29	Sun S, Zhang C, Gao J, Qin Q, Zhang Y, Zhu H, Yang X, Yang D and Yan HT: Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells. Toxicol Ind Health. 34:270–281. 2018. View Article : Google Scholar : PubMed/NCBI
30	Taofiq O, Rodrigues F, Barros L, et al: Agaricus blazei Murrill from Brazil: an ingredient for nutraceutical and cosmeceutical applications. Food Funct. 10:565–572. 2019. View Article : Google Scholar : PubMed/NCBI
31	Wang H, Fu Z and Han C: The medicinal values of culinary-medicinal royal sun mushroom (Agaricus blazei Murrill). Evid Based Complement Alternat Med. 2013:8426192013. View Article : Google Scholar : PubMed/NCBI
32	Wu S, Li F, Jia S, et al: Drying effects on the antioxidant properties of polysaccharides obtained from Agaricus blazei Murrill. Carbohydr Polym. 103:414–417. 2014. View Article : Google Scholar : PubMed/NCBI
33	Zhang F, Song X, Li L, Wang J, Lin L, Li C, Li H, Lv Y, Jin Y, Liu Y, et al: Polygala tenuifolia polysaccharide PTP induced apoptosis in ovarian cancer cells via a mitochondrial pathway. Tumor Biol. 36:2913–2919. 2015. View Article : Google Scholar
34	Schultz DR and Harringto WJ: Apoptosis: Programmed cell death at a molecular level. Semin Arthritis Rheum. 32:345–369. 2003. View Article : Google Scholar : PubMed/NCBI
35	Mondal A, Banerjee D, Majumder R, Maity TK and Khowala S: Evaluation of in vitro antioxidant, anticancer and in vivo antitumour activity of Termitomyces clypeatus MTCC 5091. Pharm Biol. 54:2536–2546. 2016. View Article : Google Scholar : PubMed/NCBI
36	Hou YC, Chao YJ, Tung HL, Wang HC and Shan YS: Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma. Cancer. 120:2766–2777. 2014. View Article : Google Scholar : PubMed/NCBI
37	Wu Q, Yang Y, Wu S, et al: Evaluation of the correlation of KAI1/CD82, CD44, MMP7 and β-catenin in the prediction of prognosis and metastasis in colorectal carcinoma. Diagn Pathol. 10:1762015. View Article : Google Scholar : PubMed/NCBI
38	Yao H, Ashihara E and Maekawa T: Targeting the Wnt/β-catenin signaling pathway in human cancers. Expert Opin Ther Targets. 15:873–887. 2011. View Article : Google Scholar : PubMed/NCBI
39	Collin-Hansen C, Pedersen SA, Andersen RA and Steinnes E: First report of phytochelatins in a mushroom: induction of phytochelatins by metal exposure in Boletus edulis. Mycologia. 99:161–174. 2007. View Article : Google Scholar : PubMed/NCBI
40	Saadeddin A, Babaei-Jadidi R, Spencer-Dene B and Nateri A: The links between Transcription, -catenin/JNK signaling, and carcinogenesis. Mol Cancer Res. 7:1189–1196. 2009. View Article : Google Scholar : PubMed/NCBI
41	Gan X, Wang J, Xi Y, Wu Z, Li Y and Li L: Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction. J Cell Biol. 180:1087–1100. 2008. View Article : Google Scholar : PubMed/NCBI
42	Lepourcelet M, Chen YNP, France DS, et al: Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell. 5:91–102. 2004. View Article : Google Scholar : PubMed/NCBI
43	Silverberg E and Lubera J: Cancer statistics, 1987. CA Cancer J Clin. 37:2–19. 1987. View Article : Google Scholar : PubMed/NCBI
44	Chairoungdua A, Smith DL, Pochard P, Hull M and Caplan MJ: Exosome release of β-catenin: A novel mechanism that antagonizes Wnt signaling. J Cell Biol. 190:1079–1091. 2010. View Article : Google Scholar : PubMed/NCBI
45	Kim JS, Crooks H, Foxworth A and Waldman T: Proof-of-principle: Oncogenic β-catenin is a valid molecular target for the development of pharmacological inhibitors 1. Mol Cancer Ther. 1:1355–1359. 2002.PubMed/NCBI
46	Liu N, Zang S, Liu Y, et al: FZD7 regulates BMSCs-mediated protection of CML cells. Oncotarget. 7:6175–6187. 2015. View Article : Google Scholar
47	Iwasaki H and Akashi K: Identification and biology of CML stem cells. Springer; Japan: 2016, doi:10.1007/978-4-431-55714-2_1. View Article : Google Scholar
48	Sun J, Li B, Jia Z, Zhang A, Wang G, Chen Z, Shang Z, Zhang C, Jian C and Yang W: RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway. J Neurooncol. 140:15–26. 2018. View Article : Google Scholar : PubMed/NCBI
49	Hoffmann VS, Hasford J, Deininger M, Cortes J, Baccarani M and Hehlmann R: Systematic review and meta-analysis of standard-dose imatinib vs. high-dose imatinib and second generation tyrosine kinase inhibitors for chronic myeloid leukemia. J Cancer Res Clin Oncol. 143:1311–1318. 2017. View Article : Google Scholar : PubMed/NCBI
50	Ge L, Tian JH, Li YN, Pan JX, Li G, Wei D, Xing X, Pan B, Chen YL, Song FJ, et al: Association between prospective registration and overall reporting and methodological quality of systematic reviews: A meta-epidemiological study. J Clin Epidemiol. 93:45–55. 2018. View Article : Google Scholar : PubMed/NCBI
51	Tian J, Zhang J, Ge L, Yang K and Song F: The methodological and reporting quality of systematic reviews from China and the USA are similar. J Clin Epidemiol. 85:50–58. 2017. View Article : Google Scholar : PubMed/NCBI
52	Sun J, Li B, Jia Z, Zhang A, Wang G, Chen Z, Shang Z, Zhang C, Cui J and Yang W: RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway. J Neurooncol. 140:15–26. 2018. View Article : Google Scholar : PubMed/NCBI
53	Liu ZL, Hu J, Huang ZL, Li H, Liu Y and Feng WL: Influence of AKT inhibitor on Wnt/β-catenin pathway in chronic myeloid leukemia K562 cells. Medical Journal of Chinese People's Liberation Army. 40:710–715. 2015.
54	Zhang L, Xu J, Zhang X, Zhang Y, Wang L, Huang X and Xu Z: The role of tumoral FOXP3 on cell proliferation, migration, and invasion in gastric cancer. Cell Physiol Biochem. 42:1739–1754. 2017. View Article : Google Scholar : PubMed/NCBI
55	Srivastava R, Cao Z, Nedeva C, et al: BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals. Proc Natl Acad Sci USA. 116:15469–15474. 2019. View Article : Google Scholar : PubMed/NCBI
56	Tajadura V, Hansen MH, Smith J, et al: β-catenin promotes endothelial survival by regulating eNOS activity and flow-dependent anti-apoptotic gene expression. Cell Death Dis. 11:4932020. View Article : Google Scholar : PubMed/NCBI
57	Liang J, Wang W, Wei L, Gao S and Wang Y: Oridonin inhibits growth and induces apoptosis of human neurocytoma cells via the Wnt/β-catenin pathway. Oncol Lett. 16:3333–3340. 2018.PubMed/NCBI
58	Sumiya T, Ikeda Y, Broadmeadow A, May K, Pritchard L, Horne C and Burlinson B: Himematsutake (Iwade Strain 101) extract (ABM-FD): Genetic toxicology and a 3-month dietary toxicity study in rats. Food Chem Toxicol. 46:1949–1959. 2008. View Article : Google Scholar : PubMed/NCBI