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Icariin has been reported to possess high anticancer activity. Colon carcinoma is one of the leading causes of cancer-related mortality worldwide. Here, the anticancer activity of icariin against HCT116 colon carcinoma cells and the possible underlying mechanism were studied. The trypan blue staining assay, wound healing assay, clonogenic assay, CCK-8 assay, and Annexin V-FITC/PI double staining method were carried out to determine the changes of HCT116 cell growth and migration. mRNA and protein expressions were determined by quantitative real-time PCR and western blot, respectively. Moreover, small interfering RNA (siRNA) plasmid was used to examine the role of p53 in icariin-induced apoptosis in HCT116 cells. Icariin significantly suppressed colon carcinoma HCT116 cells by decreasing migration and viability, and simultaneously promoting apoptosis. Icariin exerted the anti-tumor effect in a dose-dependent manner by up-regulating p53. During treatment of icariin, p-p53, p21, and Bax levels increased, and Bcl-2 level decreased. Short time treatment with icariin induced DNA damage in HCT116 cells. Furthermore, the cytotoxicity of icariin was decreased after p53 knockdown or by using caspase inhibitors. p53 was involved in activities of caspase-9 and caspase-3. Icariin repressed colon carcinoma cell line HCT116 by enhancing p53 expression and activating p53 functions possibly through Bcl-2/Bax imbalance and caspase-9 and -3 regulation. Icariin treatment also induced DNA damage in HCT116 cells.

Titel:	Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities.
Autor/in / Beteiligte Person:	Tian, M ; Yang, S ; Yan, X
Link:	Zum Volltext
Zeitschrift:	Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, Jg. 51 (2018-08-06), Heft 10, S. e7151
Veröffentlichung:	[SP, Brasil : Associação Brasileira de Divulgação Científica, 1981-, 2018
Medientyp:	academicJournal
ISSN:	1414-431X (electronic)
DOI:	10.1590/1414-431X20187151
Schlagwort:	Blotting, Western Colonic Neoplasms metabolism HCT116 Cells Humans RNA, Small Interfering Real-Time Polymerase Chain Reaction Tumor Suppressor Protein p53 metabolism Antineoplastic Agents, Phytogenic pharmacology Apoptosis drug effects Cell Movement drug effects Cell Proliferation drug effects Colonic Neoplasms pathology Flavonoids pharmacology Tumor Suppressor Protein p53 drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Braz J Med Biol Res] 2018 Aug 06; Vol. 51 (10), pp. e7151. <i>Date of Electronic Publication: </i>2018 Aug 06. MeSH Terms: Antineoplastic Agents, Phytogenic / pharmacology ; Apoptosis / drug effects ; Cell Movement / drug effects ; Cell Proliferation / drug effects ; Colonic Neoplasms / pathology ; Flavonoids / pharmacology ; Tumor Suppressor Protein p53 / *drug effects ; Blotting, Western ; Colonic Neoplasms / metabolism ; HCT116 Cells ; Humans ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Tumor Suppressor Protein p53 / metabolism References: Environ Toxicol Pharmacol. 2017 Sep;54:7-13. (PMID: 28667862) ; Apoptosis. 2007 Sep;12(9):1721-31. (PMID: 17520193) ; Cell Biochem Biophys. 2014 Jul;69(3):523-30. (PMID: 24435883) ; Oncol Rep. 2015 Jun;33(6):2829-36. (PMID: 25845681) ; Eur J Pharmacol. 2010 Jun 10;635(1-3):40-8. (PMID: 20307526) ; Cell. 1994 Aug 26;78(4):703-11. (PMID: 8069917) ; Cold Spring Harb Perspect Med. 2017 May 1;7(5):null. (PMID: 28270530) ; PLoS One. 2013 Nov 14;8(11):e80784. (PMID: 24244715) ; Oncogene. 1993 Feb;8(2):307-18. (PMID: 8426740) ; Zhonghua Xin Xue Guan Bing Za Zhi. 2016 Aug 24;44(8):707-13. (PMID: 27545131) ; Nat Rev Cancer. 2009 Oct;9(10):714-23. (PMID: 19730431) ; Exp Cell Res. 2017 Sep 15;358(2):227-233. (PMID: 28663058) ; Annu Rev Pharmacol Toxicol. 2009;49:223-41. (PMID: 18834305) ; Pharmacol Rep. 2017 Dec;69(6):1270-1281. (PMID: 29128809) ; Cell. 1995 Jan 27;80(2):293-9. (PMID: 7834749) ; Science. 2004 Feb 6;303(5659):844-8. (PMID: 14704432) ; Eur J Pharmacol. 2007 Jun 14;564(1-3):26-36. (PMID: 17382317) ; Curr Cancer Drug Targets. 2017 Jun 23;:null. (PMID: 28669344) ; Oncotarget. 2017 Jul 4;8(27):45031. (PMID: 28693126) ; Cell Biochem Biophys. 2015 Sep;73(1):213-9. (PMID: 25721870) ; Biomed Pharmacother. 2017 Apr;88:823-831. (PMID: 28171848) ; Cell Biochem Biophys. 2014 Jun;69(2):303-10. (PMID: 24590261) ; Biol Pharm Bull. 2015;38(2):277-84. (PMID: 25747987) ; Nat Rev Cancer. 2009 Nov;9(11):821-9. (PMID: 19776747) ; Cancer Cell. 2009 Mar 3;15(3):171-83. (PMID: 19249676) ; Surgery. 2015 Oct;158(4):981-6; discussion 986-7. (PMID: 26189069) ; Mol Cell. 1997 Dec;1(1):3-11. (PMID: 9659898) Substance Nomenclature: 0 (Antineoplastic Agents, Phytogenic) ; 0 (Flavonoids) ; 0 (RNA, Small Interfering) ; 0 (Tumor Suppressor Protein p53) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20180809 Date Completed: 20180907 Latest Revision: 20181114 Update Code: 20240513 PubMed Central ID: PMC6086551

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Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities.