nach oben

Erschienen in:

29.03.2018 | Original Article

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

verfasst von: 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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

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.

Siegel RL, Miller KD, Jemal A (2017) Cancer statistics 2017. CA Cancer J Clin 67(1):7–30CrossRefPubMed

Torre LA et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108CrossRefPubMed

Miller KD et al (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66(4):271–289CrossRefPubMed

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

Frank NY, Schatton T, Frank MH (2010) The therapeutic promise of the cancer stem cell concept. J Clin Invest 120(1):41–50CrossRefPubMedPubMedCentral

Islam F et al (2015) Cancer stem cell: fundamental experimental pathological concepts and updates. Exp Mol Pathol 98(2):184–191CrossRefPubMed

O’Brien CA et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110CrossRefPubMed

Dalerba P et al (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104(24):10158–10163CrossRefPubMedPubMedCentral

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.

Huang EH, Wicha MS (2008) Colon cancer stem cells: implications for prevention and therapy. Trends Mol Med 14(11):503–509CrossRefPubMedPubMedCentral

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.

Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127(3):469–480CrossRefPubMed

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.

Wang L et al (2014) Enrichment and characterization of cancer stemlike cells from a cervical cancer cell line. Mol Med Rep 9(6):2117–2123CrossRefPubMedPubMedCentral

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.

Zhu YT et al (2016) A modified method by differential adhesion for enrichment of bladder cancer stem cells. Int Braz J Urol 42(4):817–824CrossRefPubMedPubMedCentral

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.

Li Y et al (2010) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res 16(9):2580–2590CrossRefPubMedPubMedCentral

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.

Zhao C et al (2007) Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 12(6):528–541CrossRefPubMedPubMedCentral

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

Titel: Wnt/β-catenin signaling mediates the suppressive effects of diallyl trisulfide on colorectal cancer stem cells
verfasst von: 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
Publikationsdatum: 29.03.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2018
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3565-0

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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