Cellular Behavior of Colchicum troodi Treated Primary and Metastatic Colon Adenocarcinoma Cell Lines Colchicum troodi and Colon Cancer

Main Article Content

Dudu Özkum Yavuz
Eda Becer
Hafize Seda Vatansever
Hilal Kabadayı
Azmi Hanoğlu
Filiz Meriçli
Ali Hikmet Meriçli

Keywords

Colchicum troodi, colon, cancer, signaling pathways

Abstract

Colchicum troodi belongs to Colchicaceae family that particularly rich in flavonoids, phenolic acids, tannin, fatty acids and alkaloids such as colchicine. The aim of this study was to investigate the anti-proliferative and protective effects of Colchicum troodi ethanolic extract toward relevant molecular signalling pathways on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines. Colchicum troodi was collected and extracted. Different concentrations of Colchicum troodi extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. Anticancer and antiprolifetarive activities of Colchicum troodi were investigated by immunocytochemistry using antibodies directed against to -catenin, LGR5, jagged 1, IHH, CD133 and Ki-67 in Colo-320 and Colo-741 cells. In the MTT assay, 10 µg/ml and 5 µg/ml Colchicum troodi extract were found to be active against Colo-741 and Colo-320 cells, respectively. Colchicum troodi extract significantly increased caspase β-catenin immunoreactivities while IHH immunostaining intensity was decreased in Colo-741 cells. We conclude that Colchicum troodi extract increased β-catenin via Wnt/β-catenin pathway in Colo-741 cells. Interestingly, it decreased IHH immunoreactivities which is an antagonist of constitutive activity of Wnt/ β-catenin signaling and is assumed to play protective act during carcinogenesis.

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References

1. Brenner H, Chen C. The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention. British Journal of Cancer 2018;119:785-792.
2. Biswas S, Davis H, Irshad S, Sandberg T, Worthley D, Leedham S. Microenvironmental control of stem cell fate in intestinal homeostasis and disease. The Journal of Pathology 2015;237(2):135-45.
3. Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V. Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Translational Medicine. 2017;6(12):2115-25.
4. Elamin MH, Shinwari Z, Hendrayani SF, Al‐Hindi H, Al‐Shail E, Khafaga Y, et al. Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center. 2010;49(3):302-14.
5. Dandawate P, Padhye S, Ahmad A, Sarkar FH. Novel strategies targeting cancer stem cells through phytochemicals and their analogs. Drug Delivery and Translational Research 2013;3:165-182.
6. Potten CS, Morris RJ. Epithelial stem cells in vivo. J Cell Sci 1998;10:45-62.
7. Farin HF, Jordens I, Mosa MH, Basak O, Korving J, Tauriello DV, et al., Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 2016; 530:340-343.
8. Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S. Notch signals control the fate of immature progenitor cells in the intestine. Nature 2005; 435:964-968.
9. Büller NV, Rosekrans SL, Westerlund J, van den Brink GR. Hedgehog signaling and maintenance of homeostasis in the intestinal epithelium. Physiology 2012;27:148-155.
10. Viney DE. An illustrated flora of North Cyprus. Koeltz Scientific Books; 1994.
11. Manning J, Felix F, Vinnersten A. The genus Colchicum L. redefined to include Androcymbium Willd. based on molecular evidence. Taxon 2007;56:872-882.
12. Alexiou S. The genus Colchicum L.(Colchicaceae) in Greece. Parnassiana Archives 2013;1:59-73.
13. Evans WC. Trease and Evans. Pharmacognosy, 9th Edition published by Saunders Elsevier. 2002:553-7.
14. Dasgeb B, Kornreich D, McGuinn K, Okon L, Brownell I, Sackett DL. Colchicine: an ancient drug with novel applications. British Journal of Dermatology. 2018;178(2):350-356.
15. Bombardelli E, Gabetta B, inventors; Indena SpA, assignee. Colchicine derivatives, the use thereof and formulations containing them. United States patent US 5,880,160. 1999 Mar 9.
16. Yang LX, inventor; California Pacific Medical Center Research Institute, Catholic Healthcare West, assignee. Colchicine derivatives. United States patent US 6,825,236. 2004 Nov 30.
17. Le HC. The pharmacology and therapeutic aspects of colchicine, Alkaloids 2000;53:288-352.
18. Pırıldar S, Sütlüpınar N, Atasever B, Erdem-Kuruca S, Papouskova B, Šimánek V. Chemical constituents of the different parts of Colchicum baytopiorum and their cytotoxic activities on K562 and HL60 cell lines. Pharmaceutical Biology 2010;48(1):32-9.
19. Sutlupinar N, Kilincli T, Mericli AH. Colchicinoids from the Seeds of Colchicum umbrosum. Chemistry of Natural Compounds 2015;51:512-514.
20. Alali FQ, Tawaha K, El-Elimat T. Determination of (–)-demecolcine and (–)-colchicine content in selected Jordanian Colchicum species. Die Pharmazie-An International Journal of Pharmaceutical Sciences 2007;62:739-742.
21. Ondra P, Válka I, Vičar J, Sütlüpinar N, Šimánek V. Chromatographic determination of constituents of the genus Colchicum (Liliaceae). Journal of Chromatography A 1995;704:351-356.
22. Becer E, Hanoğlu DY, Kabadayı H, Hanoğlu A, Vatansever S, Yavuz DÖ, et al. The effect of Colchicum pusillum in human colon cancer cells via Wnt/β-catenin pathway. Gene 2019;686:213-219.
23. Taylor EW. The mechanism of colchicine inhibition of mitosis: I. Kinetics of inhibition and the binding of h3-colchicine. The Journal of Cell Biology 1965;25:145-160.
24. Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg–Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature 1982;299(5878):65-67.
25. Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells, Gastroenterology 2010;138:1681-1696.
26. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445(7123):111-115.
27. Watt FM. Unexpected Hedgehog–Wnt interactions in epithelial differentiation. Trends in Molecular Medicine 2004;10:577-580.
28. Fu X, Yang X, Zhao L. Indian hedgehog, a neglected member of hedgehog pathway, may offer a novel avenue for colorectal cancer therapy. Cancer Biotherapy and Radiopharmaceuticals 2009;24:733-735.
29. Büller NV, Rosekrans SL, Metcalfe C, Heijmans J, Van Dop WA, Fessler E, et al. Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice. Gastroenterology 2015;148(1):170-80.
30. Gerling M, Büller NV, Kirn LM, Joost S, Frings O, Englert B, et al. Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth. Nature communications 2016;7(1):1-7.
31. Fu X, Yang X, Li J, Tian X, Cai J, Zhang Y. Opposite expression patterns of Sonic hedgehog and Indian hedgehog are associated with aberrant methylation status of their promoters in colorectal cancers. Pathology 2010;42:553-559.
32. Van Den Brink GR, Bleuming SA, Hardwick JC, Schepman BL, Offerhaus GJ, Keller JJ, et al. Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nature Genetics 2004;36(3):277-282.

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