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Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo . Cuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa.

Competing Interests: The authors declare no conflict of interest.

Titel:	Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer).
Autor/in / Beteiligte Person:	Sikander, M ; Malik, S ; Khan, S ; Kumari, S ; Chauhan, N ; Khan, P ; Halaweish, FT ; Chauhan, B ; Yallapu, MM ; Jaggi, M ; Chauhan, SC
Link:	Volltext (PDF)
Zeitschrift:	Cells, Jg. 9 (2019-12-31), Heft 1
Veröffentlichung:	Basel, Switzerland : MDPI, 2019
Medientyp:	academicJournal
ISSN:	2073-4409 (electronic)
DOI:	10.3390/cells9010103
Schlagwort:	Animals Antineoplastic Agents, Phytogenic administration & dosage Antineoplastic Agents, Phytogenic chemistry Antineoplastic Agents, Phytogenic pharmacokinetics Apoptosis drug effects Cell Cycle drug effects Cell Line, Tumor Cell Movement drug effects Cell Proliferation drug effects Deoxycytidine analogs & derivatives Deoxycytidine pharmacology Disease Models, Animal Drug Resistance, Neoplasm Gene Expression Regulation drug effects Humans Mice Models, Molecular Mucins genetics Mucins metabolism Pancreatic Neoplasms Structure-Activity Relationship Triterpenes administration & dosage Triterpenes chemistry Triterpenes pharmacokinetics Xenograft Model Antitumor Assays Gemcitabine Antineoplastic Agents, Phytogenic pharmacology Triterpenes pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Cells] 2019 Dec 31; Vol. 9 (1). <i>Date of Electronic Publication: </i>2019 Dec 31. MeSH Terms: Antineoplastic Agents, Phytogenic / pharmacology ; Triterpenes / pharmacology ; Animals ; Antineoplastic Agents, Phytogenic / administration & dosage ; Antineoplastic Agents, Phytogenic / chemistry ; Antineoplastic Agents, Phytogenic / pharmacokinetics ; Apoptosis / drug effects ; Cell Cycle / drug effects ; Cell Line, Tumor ; Cell Movement / drug effects ; Cell Proliferation / drug effects ; Deoxycytidine / analogs & derivatives ; Deoxycytidine / pharmacology ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Gene Expression Regulation / drug effects ; Humans ; Mice ; Models, Molecular ; Mucins / genetics ; Mucins / metabolism ; Pancreatic Neoplasms ; Structure-Activity Relationship ; Triterpenes / administration & dosage ; Triterpenes / chemistry ; Triterpenes / pharmacokinetics ; Xenograft Model Antitumor Assays ; Gemcitabine References: Sci Rep. 2016 Nov 08;6:36594. (PMID: 27824155) ; Oncotarget. 2014 Sep 15;5(17):7599-609. (PMID: 25277192) ; Int J Cancer. 2009 Jan 1;124(1):46-54. (PMID: 18821582) ; Cancer Biol Ther. 2007 Apr;6(4):481-6. (PMID: 18027437) ; CA Cancer J Clin. 2018 Jan;68(1):7-30. (PMID: 29313949) ; J Mol Biol. 1963 Jul;7:95-9. (PMID: 13990617) ; Cell Prolif. 2003 Jun;36(3):131-49. (PMID: 12814430) ; Cancer. 2011 Jun 15;117(12):2735-46. (PMID: 21656752) ; Nat Prod Rep. 2005 Jun;22(3):386-99. (PMID: 16010347) ; Expert Opin Ther Targets. 2011 Jul;15(7):817-28. (PMID: 21391891) ; Mol Pharm. 2007 Nov-Dec;4(6):803-6. (PMID: 18052085) ; Cancer Lett. 2013 Dec 1;341(2):166-77. (PMID: 23920124) ; Curr Opin Biotechnol. 2014 Dec;30:230-7. (PMID: 25260043) ; Biofactors. 2009 Nov-Dec;35(6):509-27. (PMID: 19904814) ; Cancer Lett. 2012 Oct 1;323(1):29-40. (PMID: 22475682) ; Nat Rev Cancer. 2009 Dec;9(12):874-85. (PMID: 19935676) ; Cancers (Basel). 2019 Mar 14;11(3):. (PMID: 30875788) ; Methods Mol Biol. 2015;1263:243-50. (PMID: 25618350) ; Mol Cancer Ther. 2012 Jan;11(1):24-33. (PMID: 22027689) ; Carcinogenesis. 2009 Dec;30(12):2085-94. (PMID: 19843642) ; Curr Pharm Des. 2012;18(17):2472-81. (PMID: 22372499) ; Int J Oncol. 2009 Apr;34(4):881-95. (PMID: 19287945) ; Int Immunopharmacol. 2009 Apr;9(4):508-13. (PMID: 19185617) ; Mol Cell Biochem. 2015 Nov;409(1-2):33-43. (PMID: 26169986) ; N Engl J Med. 2011 May 12;364(19):1817-25. (PMID: 21561347) ; Evid Based Complement Alternat Med. 2013;2013:975350. (PMID: 24194785) ; Asian Pac J Cancer Prev. 2011;12(10):2513-6. (PMID: 22320949) ; Int Immunopharmacol. 2013 Dec;17(4):1044-50. (PMID: 24140411) ; Sci Rep. 2016 Feb 03;6:20051. (PMID: 26837852) ; Nat Rev Cancer. 2010 Oct;10(10):683-95. (PMID: 20814421) ; Tumour Biol. 2013 Feb;34(1):285-91. (PMID: 23150173) ; J Nat Prod. 2015 Apr 24;78(4):873-9. (PMID: 25756299) ; Cancer Res. 2014 Jun 1;74(11):2913-21. (PMID: 24840647) ; J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576) ; Sci Rep. 2019 Feb 8;9(1):1676. (PMID: 30737440) ; Expert Rev Mol Diagn. 2010 Jul;10(5):591-601. (PMID: 20629509) ; Methods Mol Biol. 2017;1654:39-54. (PMID: 28986782) ; Nat Rev Gastroenterol Hepatol. 2009 Jul;6(7):412-22. (PMID: 19506583) ; Oncol Rep. 2015 Jan;33(1):383-90. (PMID: 25394408) ; Oncol Rep. 2018 Jun;39(6):2595-2603. (PMID: 29658590) ; Protoplasma. 2013 Apr;250(2):483-93. (PMID: 22772591) ; Med Oncol. 2016 Apr;33(4):30. (PMID: 26913856) ; Mol Cancer Ther. 2010 May;9(5):1419-31. (PMID: 20423995) ; Cancer Lett. 2003 Jan 10;189(1):11-6. (PMID: 12445672) ; Otol Neurotol. 2013 Oct;34(8):1519-27. (PMID: 23928514) ; BMC Biol. 2007 May 08;5:17. (PMID: 17488521) Grant Information: W81XWH-14-1-0154 DOD; R01 CA204552 United States CA NCI NIH HHS; R01 CA210192 United States CA NCI NIH HHS; R01 CA206069 United States CA NCI NIH HHS; R01CA142736, U01CA162106, K22CA1744841 United States GF NIH HHS Contributed Indexing: Keywords: cucurbitacin D; miR-145 and MUC13; mucin; pancreatic cancer Substance Nomenclature: 0 (Antineoplastic Agents, Phytogenic) ; 0 (MUC13 protein, human) ; 0 (Mucins) ; 0 (Triterpenes) ; 0W860991D6 (Deoxycytidine) ; 5I62H4ORC7 (cucurbitacin D) ; 0 (Gemcitabine) Entry Date(s): Date Created: 20200108 Date Completed: 20200903 Latest Revision: 20221207 Update Code: 20231215 PubMed Central ID: PMC7017063

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Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer).