title: Growth inhibitory effect of Cucurbitacin E on breast cancer cells.
abstract: OBJECTIVE
  Due its inhibitory effects on chemical carcinogenesis and inflammation, Cucurbitacins have been proposed as an effective agent for the prevention or treatment of human cancers. In this study, we aimed to explore the effect of Cucurbitacin E (CuE) on human breast cancer cells.
  
  
  METHODS
  The inhibitory effect of CuE on proliferation of Bcap37 and MDA-MB-231 cells was assessed by MTT assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry (FCM). The expression of pro-caspase 3, cleaved caspase 3, p21, p27 and the phosphorylation of signaling proteins was detected by Western Blotting.
  
  
  RESULTS
  CuE inhibited the growth of human breast cancer cells in a dose and time-dependent manner. FCM analysis showed that CuE induced G2/M phase arrest and cell apoptosis. CuE treatment promoted the cleavage of caspase 3 and upregulated p21 and p27. In addition, the phosphorylation of STAT3 but not ERK-1/2 was abrogated upon CuE treatment. Interestingly, losedose CuE significantly enhanced the growth inhibition induced by cisplatin. Conclusions Cucurbitacin E (CuE) could inhibit the growth of human breast cancer cells in vitro. CuE induced both apoptosis and cell cycle arrest probably through the inhibition of STAT3 function. Lose-dose CuE significantly enhanced the growth inhibitory effect of cisplatin on breast cancer cells, further indicating the potential clinical values of CuE for the prevention or treatment of human breast cancer.
authors.affiliation: Department of Medical Oncology, the key laboratory of Integrated Chinese and Western Medical Oncology in Zhejiang Province, Zhejiang Cancer Hospital HangZhou, China 310022 ; Department of Medical Oncology, Institute of Clinical Science, Sir Runrun Shaw Hospital, Medical College of Zhejiang University Hangzhou, China 310003.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.forename: Linling
authors.initials: L
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Liu
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
authors.forename: Weimin
authors.initials: W
authors.lastname: Mao
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D010766:Phosphorylation; D000091402:Prohibitins; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000717331:PHB2 protein, human; D000091402:Prohibitins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D002945:Cisplatin; C102326:cucurbitacin E
keywords: Cucurbitacin E; apoptosis; breast cancer
references.citation: J Cancer Res Clin Oncol. 2010 Apr;136(4):603-10
references.pmid: 19816711
references.citation: J Nat Prod. 2000 Sep;63(9):1300-2
references.pmid: 11000045
references.citation: Environ Toxicol Pharmacol. 2012 Mar;33(2):245-51
references.pmid: 22245841
references.citation: Apoptosis. 2012 Jan;17(1):79-89
references.pmid: 21928090
references.citation: Cancer Res. 2009 Jul 15;69(14):5876-84
references.pmid: 19605406
references.citation: Int J Health Sci (Qassim). 2013 Jan;7(1):77-89
references.pmid: 23559908
references.citation: Acta Biochim Biophys Sin (Shanghai). 2012 Jan;44(1):70-9
references.pmid: 22194015
references.citation: Cancer Chemother Pharmacol. 2012 Sep;70(3):415-24
references.pmid: 22814677
references.citation: Int J Cancer. 2008 Sep 15;123(6):1364-75
references.pmid: 18561312
references.citation: Biochem Pharmacol. 1996 Nov 22;52(10):1553-60
references.pmid: 8937470
references.citation: Int J Pharm. 2010 Jan 4;383(1-2):186-91
references.pmid: 19732815
references.citation: Mol Pharmacol. 2013 May;83(5):1141-54
references.pmid: 23478800
references.citation: Am J Transl Res. 2012;4(1):44-51
references.pmid: 22347521
references.citation: Oncogene. 2005 May 5;24(20):3236-45
references.pmid: 15735720
references.citation: Cancer. 2011 Jun 15;117(12):2735-46
references.pmid: 21656752
references.citation: Anticancer Drugs. 2012 Sep;23(8):777-87
references.pmid: 22561419
references.citation: Nat Prod Rep. 2005 Jun;22(3):386-99
references.pmid: 16010347
references.citation: PLoS One. 2013;8(2):e55732
references.pmid: 23393598
references.citation: Eur J Pharmacol. 2008 Jun 10;587(1-3):78-84
references.pmid: 18442812
references.citation: Carcinogenesis. 2010 Dec;31(12):2097-104
references.pmid: 20732905