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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2018

01-06-2018 | Original Article

Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells

Authors: Qi Zhang, Xiao-Ting Li, Yue Chen, Jia-Qi Chen, Jian-Yun Zhu, Yu Meng, Xiao-Qian Wang, Yuan Li, Shan-Shan Geng, Chun-Feng Xie, Jie-Shu Wu, Cai-Yun Zhong, Hong-Yu Han

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2018

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Abstract

Purpose

Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) initiation, growth, and metastasis. Garlic-derived organosulfur compound diallyl trisulfide (DATS) possesses cancer suppressive properties. Wnt/β-catenin signaling is a key target for CSCs inhibition. However, the interventional effect of DATS on colorectal CSCs has not been clarified. We aimed to illustrate the regulation of Wnt/β-catenin in DATS-induced colorectal CSCs inhibition.

Methods

Serum-free medium culture was used to enrich colorectal CSCs. SW480 and DLD-1 sphere-forming cells were treated with different concentrations of DATS for 5 days; LiCl and β-catenin plasmids were used to stimulate the activity of Wnt/β-catenin pathway. The size and number of colonspheres were detected by tumorsphere formation assay; the expression of colorectal CSCs-related genes was detected by Western blotting and qRT-PCR; the capacities of colorectal CSCs proliferation and apoptosis were detected by Cell Counting Kit-8, Hoechst 33258 cell staining and flow cytometry, respectively.

Results

The levels of colorectal CSCs markers were elevated in the tumorspheres cells. DATS efficiently suppressed the activity of colorectal CSCs, as evidenced by reducing the size and number of colonspheres, decreasing the expression of colorectal CSCs markers, promoting apoptosis and inhibiting the proliferation of colorectal CSCs. Moreover, DATS suppressed the activity of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effect of DATS on colorectal CSCs.

Conclusions

Wnt/β-catenin pathway mediates DATS-induced colorectal CSCs suppression. These findings support the use of DATS for targeting colorectal CSCs.
Literature
1.
2.
3.
Miller KD et al (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66(4):271–289CrossRefPubMed
4.
Thomassen I et al (2013) Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin. Dis Colon Rectum 56(12):1373–1380CrossRefPubMed
5.
6.
Islam F et al (2015) Cancer stem cell: fundamental experimental pathological concepts and updates. Exp Mol Pathol 98(2):184–191CrossRefPubMed
7.
O’Brien CA et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110CrossRefPubMed
8.
9.
Clarke MF et al (2006) Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344CrossRefPubMed
10.
11.
Zeuner A et al (2014) Colorectal cancer stem cells: from the crypt to the clinic. Cell Stem Cell 15(6):692–705CrossRefPubMed
12.
Holland JD et al (2013) Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol 25(2):254–264CrossRefPubMed
13.
14.
Tang X et al (2017) Upregulation of GNL3 expression promotes colon cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/beta-catenin signaling pathway. Oncol Rep 38(4):2023–2032CrossRefPubMedPubMedCentral
15.
Wang G et al (2017) Cyclophilin A maintains glioma-initiating cell stemness by regulating Wnt/beta-catenin signaling. Clin Cancer Res 23(21):6640–6649CrossRefPubMed
16.
Lai KC et al (2013) Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase-2, -7, and -9 expressions. Environ Toxicol 28(9):479–488CrossRefPubMed
17.
Wang HC et al (2017) Diallyl trisulfide inhibits cell migration and invasion of human melanoma a375 cells via inhibiting integrin/facal adhesion kinase pathway. Environ Toxicol 32(11):2352–2359CrossRefPubMed
18.
Jiang XY et al (2017) Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment. Acta Pharmacol Sin 38(7):1048–1058CrossRefPubMedPubMedCentral
19.
Yu CS et al (2012) Diallyl trisulfide induces apoptosis in human primary colorectal cancer cells. Oncol Rep 28(3):949–954CrossRefPubMed
20.
Wu PP et al (2011) Diallyl trisulfide (DATS) inhibits mouse colon tumor in mouse CT-26 cells allograft model in vivo. Phytomedicine 18(8–9):672–676CrossRefPubMed
21.
Dotse E, Bian Y (2016) Isolation of colorectal cancer stem-like cells. Cytotechnology 68(4):609–619CrossRefPubMed
22.
Melin C et al (2014) Sedimentation field flow fractionation monitoring of in vitro enrichment in cancer stem cells by specific serum-free culture medium. J Chromatogr B Analyt Technol Biomed Life Sci 963:40–46CrossRefPubMed
23.
Boman BM, Wicha MS (2008) Cancer stem cells: a step toward the cure. J Clin Oncol 26(17):2795–2799CrossRefPubMed
24.
Wicha MS, Liu SL, Dontu G (2006) Cancer stem cells: an old idea—a paradigm shift. Can Res 66(4):1883–1890CrossRef
25.
Ricci-Vitiani L et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115CrossRefPubMed
26.
Kozovska Z, Gabrisova V, Kucerova L (2014) Colon cancer: cancer stem cells markers, drug resistance and treatment. Biomed Pharmacother 68(8):911–916CrossRefPubMed
27.
Du L et al (2008) CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 14(21):6751–6760CrossRefPubMed
28.
Cho SH et al (2012) CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion. Int J Oncol 41(1):211–218PubMed
29.
Huang EH et al (2009) Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Can Res 69(8):3382–3389CrossRef
30.
Carpentino JE et al (2009) Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. Cancer Res 69(20):8208–8215CrossRefPubMedPubMedCentral
31.
Kashyap V et al (2009) Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev 18(7):1093–1108CrossRefPubMedPubMedCentral
32.
Amini S et al (2014) The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anat Cell Biol 47(1):1–11CrossRefPubMedPubMedCentral
33.
34.
Hashimoto N et al (2014) Cancer stem-like sphere cells induced from de-differentiated hepatocellular carcinoma-derived cell lines possess the resistance to anti-cancer drugs. BMC Cancer 14:722CrossRefPubMedPubMedCentral
35.
36.
Wang L et al (2013) Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci 9(5):472–479CrossRefPubMedPubMedCentral
37.
38.
Marquardt JU et al (2015) Curcumin effectively inhibits oncogenic NF-kappaB signaling and restrains stemness features in liver cancer. J Hepatol 63(3):661–669CrossRefPubMedPubMedCentral
39.
Zhu J et al (2017) Wnt/beta-catenin pathway mediates (−)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells. Biochem Biophys Res Commun 482(1):15–21CrossRefPubMed
40.
Lim KJ et al (2011) A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. Cancer Biol Ther 11(5):464–473CrossRefPubMedPubMedCentral
41.
42.
Zhu J et al (2017) miR-19 targeting of GSK3beta mediates sulforaphane suppression of lung cancer stem cells. J Nutr Biochem 44:80–91CrossRefPubMed
43.
Chikazawa N et al (2010) Inhibition of Wnt signaling pathway decreases chemotherapy-resistant side-population colon cancer cells. Anticancer Res 30(6):2041–2048PubMed
Metadata
Title
Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells
Authors
Qi Zhang
Xiao-Ting Li
Yue Chen
Jia-Qi Chen
Jian-Yun Zhu
Yu Meng
Xiao-Qian Wang
Yuan Li
Shan-Shan Geng
Chun-Feng Xie
Jie-Shu Wu
Cai-Yun Zhong
Hong-Yu Han
Publication date
01-06-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3565-0

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