Research Article
Year 2022,
Volume: 32 Issue: 4, 372 - 379, 31.08.2022
Abstract
AMAÇ: Kolon kanseri dünya çapında ana sağlık problemlerinin başında gelmektedir. Kanser kök hücreleri (CSC'ler), tümör heterojenitesi ve dormansisinde yer alan tümör başlatan hücreler olarak adlandırılır. CSC'ler ilaç direncine, metastaza ve primer ve metastatik kanserlerin nüksetmesine neden olabilir. Kolon kanser kök hücrelerinin digger hücreler ile olan etkileşimlerive hayatta kalma eğilimleri etkili tedavi için alternatif bir yol olabilir. Çalışmamızda primer (HCT-116) ve metastatik (Colo-741) kolon CSC'lerinde, asteosidin kök hücre özelliği, apoptotik ve inflamatuar sürece etkilerini değerlendirmeyi amaçladık.
GEREÇ VE YÖNTEM: CSC' ler, anti-CD133 belirteci kullanılarak MINIMACS sistemi ile her iki tip kolon kanseri hücre hattından elde edildi. Metastatik Colo-741 ve non-metastatik HCT-116 CD133+ ve CD133- hücreleri, 48 saat boyunca Acteosid olmadan veya Acteosid ile culture edildi. Apoptoz için Kaspaz-3, Bcl, Bax, ve Fas-L, inflamasyon için IL-1β, TNF-α, IL-6, IL8 ve IL-10 proteinlerinin ifadesi indirekt immünositokimya tekniği ile H-Score yapılarak analiz edildi. Hücre morfolojisindeki değişiklikler invert mikroskop altında incelendi.
BULGULAR VE SONUÇ: Oct-4 ifadesinin hem metastatic hem de metastatik olmayan kolon kanser hücrelerinde akteosit uygulamasından sonra azaldığı görüldü. Ayrıca Colo-741 CD133+ ve CD133- hücrelerin her ikisinde de Bax/Bcl oranının yoğunluğunu arttırdı ve kaspaz 3 ifadesinin arttığı görüldü. Akteosid metastatic COLO-741 hücrelerinde inflamasyona immunohistokimyasal olarak etki etmezken, apoptotic sürece Bax/Bcl oranını değiştirerek katkıda bulunmuştur. Hücrelerin morfolojisi değerlendirildiğinde de COLO-741 CD133+ ve CD133- hücrelerde apoptotic hücrelerin sayılarının arttığı görülmüştür.
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Mali destek alınmamıştır
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Year 2022,
Volume: 32 Issue: 4, 372 - 379, 31.08.2022
Abstract
AIM: Colon cancer is one of the main health problems worldwide. Cancer stem cells (CSCs) are referred to as tumor-initiating cells involved in tumor heterogeneity and dormancy. CSCs can cause drug resistance, metastasis, and recurrence of primary and metastatic cancers. The interactions and survival trends of colon cancer stem cells with other cells may be an alternative route for effective treatment. In our study, we aimed to evaluate the effects of asteoside on stem cell properties, apoptotic and inflammatory processes in primary (HCT-116) and metastatic (Colo-741) colon CSCs.
METHERIALS AND METHODS: CSCs were obtained from both types of colon cancer cell lines with the MINIMACS system using the anti-CD133 reagent. Metastatic Colo-741 and non-metastatic HCT-116 CD133+ and CD133- cells were cultured with or without Acteoside for 48 hours. Expressions of Caspase-3, Bcl, Bax, and Fas-L for apoptosis, and IL-1β, TNF-α, IL-6, IL8 and IL-10 for inflammation were analyzed by indirect immunocytochemistry technique by performing H-Score. Changes in cell morphology were examined under an inverted microscope.
RESULTS AND CONCLUSION: It was observed that Oct-4 expression decreased after acteocyte administration in both metastatic and non-metastatic colon cancer cells. In addition, Colo-741 increased the intensity of the Bax/Bcl ratio in both CD133+ and CD133- cells and increased caspase 3 expression. While acteoside did not immunohistochemically affect inflammation in metastatic COLO-741 cells, it contributed to the apoptotic process by changing the Bax/Bcl ratio. When the morphology of the cells was evaluated, it was observed that the number of apoptotic cells increased in COLO-741 CD133+ and CD133- cells.
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- Referans 11. Salvesen GS. Caspases: opening the boxes and interpreting the arrows. Cell Death & Differentiation [Internet]. 2002 Jan 21;9(1):3–5. Available from: https://www.nature.com/articles/4400963
- Referans 12. Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, et al. Apoptosis and cancer: mutations within caspase genes. Journal of Medical Genetics [Internet]. 2009 Aug 1;46(8):497–510. Available from: https://jmg.bmj.com/lookup/doi/10.1136/jmg.2009.066944
- Referans 13. Botchkina G. Colon cancer stem cells - From basic to clinical application. Cancer Letters [Internet]. 2013;338(1):127–40. Available from: http://dx.doi.org/10.1016/j.canlet.2012.04.006
- Referans 14. Fırat F, Özgül M, Türköz Uluer E, Inan S. Effects of caffeic acid phenethyl ester (CAPE) on angiogenesis, apoptosis and oxidatıve stress ın various cancer cell lines. Biotechnic & Histochemistry [Internet]. 2019 Oct 3;94(7):491–7. Available from: https://www.tandfonline.com/doi/full/10.1080/10520295.2019.1589574
- Referans 15. Alipieva K, Korkina L, Orhan IE, Georgiev MI. Verbascoside - A review of its occurrence, (bio)synthesis and pharmacological significance. Biotechnology Advances [Internet]. 2014;32(6):1065–76. Available from: http://dx.doi.org/10.1016/j.biotechadv.2014.07.001
- Referans 16. SK V. Ferulic acid ester from Colebrookea oppositifolia. Ind J Chem. 2012;
- Referans 17. Lee JY, Woo E, Kang KW. Screening of new chemopreventive compounds from Digitalis purpurea. Die Pharmazie. 2006 Apr;61(4):356–8.
- Referans 18. Tatematsu M, Mera Y, Inoue T, Satoh K, Sato K, Ito N. Stable phenotypic expression of glutathione S-transferase placental type and unstable phenotypic expression of gamma-glutamyltransferase in rat liver preneoplastic and neoplastic lesions. Carcinogenesis. 1988 Feb;9(2):215–20.
- Referans 19. Hwang TW, Kim DH, Kim DB, Jang TW, Kim GH, Moon M, et al. Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy. International Journal of Molecular Medicine. 2019;43(3):1478–86.
- Referans 20. Liao YF, Rao YK, Tzeng YM. Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-κB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells. Food and Chemical Toxicology [Internet]. 2012;50(8):2930–6. Available from: http://dx.doi.org/10.1016/j.fct.2012.05.033
- Referans 21. Pastore S, Potapovich A, Kostyuk V, Mariani V, Lulli D, Luca C De, et al. Plant Polyphenols Effectively Protect HaCaT Cells from Ultraviolet C – Triggered Necrosis and Suppress Inflammatory Chemokine Expression. 2009;313:305–13.
- Referans 22. Zhou L, Feng Y, Jin Y, Liu X, Sui H, Chai N, et al. Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer. BMC Cancer. 2014;14(1):1–11.
- Referans 23. Reya, T., Morrison, S. J., Clarke, M. F., & Weissman IL. Stem cells, cancer, and cancer stem cells. NATURE. 2001;414(November):197–209.
- Referans 24. Chen K, Huang Y, Chen J. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta pharmacologica Sinica. 2013 Jun;34(6):732–40.
- Referans 25. Koch U, Krause M, Baumann M. Cancer stem cells at the crossroads of current cancer therapy failures-Radiation oncology perspective. Seminars in Cancer Biology [Internet]. 2010;20(2):116–24. Available from: http://dx.doi.org/10.1016/j.semcancer.2010.02.003
- Referans 26. Eun K, Ham SW, Kim H. Cancer stem cell heterogeneity: Origin and new perspectives on CSC targeting. BMB Reports. 2017;50(3):117
- Referans 27. Ahmad R. Safa. Resistance to Cell Death and Its Modulation in Cancer Stem Cells. HHS Public Access. 2016;21(12):203–19.
- Referans 28. Cheng TC, Lu JF, Wang JS, Lin LJ, Kuo HI, Chen BH. Antiproliferation effect and apoptosis mechanism of prostate cancer cell PC-3 by flavonoids and saponins prepared from Gynostemma pentaphyllum. Journal of Agricultural and Food Chemistry. 2011;59(20):11319–
- Referans 29. Gangemi G, Gazzerro P, Fiore D, Proto MC, Butini S, Gemma S, et al. PBOX-15 induces apoptosis and improves the efficacy of oxaliplatin in human colorectal cancer cell lines. European Journal of Pharmacology [Internet]. 2013;714(1–3):379–87. Available from: http://dx.doi.org/10.1016/j.ejphar.2013.07.011
- Referans 30. Shigdar S, Li Y, Bhattacharya S, O’Connor M, Pu C, Lin J, et al. Inflammation and cancer stem cells. Cancer Letters [Internet]. 2014;345(2):271–8. Available from: http://dx.doi.org/10.1016/j.canlet.2013.07.031
- Referans 31. Kumari N, Dwarakanath BS, Das A, Bhatt AN. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumor Biology [Internet]. 2016;37(9):11553–72. Available from: http://dx.doi.org/10.1007/s13277-016-5098-7
- Referans 32. Maccalli C, Parmiani G, Ferrone S. Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy. Immunological Investigations [Internet]. 2017;46(3):221–38. Available from: http://dx.doi.org/10.1080/08820139.2017.1280051
- Referans 33. Shimizu M, Tanaka N. IL-8-induced O-GlcNAc modification via GLUT3 and GFAT regulates cancer stem cell-like properties in colon and lung cancer cells. Oncogene [Internet]. 2019;38(9):1520–33. Available from: http://dx.doi.org/10.1038/s41388-018-0533-4
- Referans 34. Yang C, Liu H, Fu Z. PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8. Cell Biology International. 2012;36(3):289–96.
- Referans 35. Kangwan N, Kim YJ, Han YM, Jeong M, Park JM, Go EJ, et al. Sonic hedgehog inhibitors prevent colitis-associated cancer via orchestrated mechanisms of IL-6/gp130 inhibition, 15-PGDH induction, Bcl-2 abrogation, and tumorsphere inhibition. Oncotarget. 2016;7(7):7667–82.
- Referans 36. Salem A, Pinto K, Koch M, Liu J, Silva EG. Are polyploid giant cancer cells in high grade serous carcinoma of the ovary blastomere-like cancer stem cells? Annals of Diagnostic Pathology [Internet]. 2020;46:151505. Available from: https://doi.org/10.1016/j.anndiagpath.2020.151505
There are 36 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Original Article |
| Authors | |
| Publication Date | August 31, 2022 |
| Submission Date | January 4, 2022 |
| Published in Issue | Year 2022 Volume: 32 Issue: 4 |
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