title: Promotion of mitotic catastrophe via activation of PTEN by paclitaxel with supplement of mulberry water extract in bladder cancer cells.
abstract: Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. Mulberry fruit is rich in phenolic compounds and flavonoids and exhibits chemopreventive activities. In this study, mulberry water extract (MWE) was used as a supplement to synergize with the effects of paclitaxel in the treatment of the TSGH 8301 human bladder cancer cell line. Treatment with paclitaxel combined with MWE (paclitaxel/MWE) enhanced the cytotoxicity of paclitaxel and induced severe G2/M arrest, mitotic catastrophe and subsequent apoptosis, as shown by MTT assay, HE staining and flow cytometry analyses. Differences in the expression and activation of Aurora A and Plk1 between cells treated with paclitaxel/MWE and paclitaxel alone suggested that the combined treatment caused a defect in the early steps of cytokinesis. Paclitaxel/MWE decreased EEA1 immunofluorescence staining and increased the expression of PTEN, indicating that the regimen inhibited the formation of the recycling endosome, which is required for cytokinesis. Paclitaxel/MWE also retarded tumor growth in a TSGH 8301 xenograft model via activation of PTEN and Caspase 3. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel through MWE supplementation by promoting mitotic catastrophe through the activation of PTEN, providing a novel and effective therapeutic option for bladder cancer treatment strategies.
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
authors.forename: Nien-Cheng
authors.initials: NC
authors.lastname: Chen
authors.affiliation: Research Institute of Biotechnology, Hung Kuang University, Taichung City, Taiwan.
authors.forename: Charng-Cherng
authors.initials: CC
authors.lastname: Chyau
authors.affiliation: Department of Pathology, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City, Taiwan.|College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
authors.forename: Hsien-Chun
authors.initials: HC
authors.lastname: Tseng
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.|Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Fen-Pi
authors.initials: FP
authors.lastname: Chou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D031625:Morus / Q000737:chemistry*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017239:Paclitaxel
references.citation: J Med Food. 2013 Oct;16(10):869-77
references.pmid: 24074296
references.citation: Microbiol Mol Biol Rev. 2002 Jun;66(2):155-78
references.pmid: 12040122
references.citation: Cell Death Dis. 2013;4:e603
references.pmid: 23598415
references.citation: Cell Death Differ. 2008 Mar;15(3):555-66
references.pmid: 18064041
references.citation: Nat Rev Mol Cell Biol. 2011 Jun;12(6):385-92
references.pmid: 21527953
references.citation: J Food Sci. 2008 Aug;73(6):H113-21
references.pmid: 19241587
references.citation: Mol Cell. 2012 Feb 24;45(4):553-66
references.pmid: 22365832
references.citation: Anal Chim Acta. 2012 Mar 16;719:87-95
references.pmid: 22340536
references.citation: Chem Biol Interact. 2012 Oct 25;200(1):38-44
references.pmid: 22982777
references.citation: J Cell Sci. 2014 Feb 15;127(Pt 4):801-11
references.pmid: 24338364
references.citation: Nat Med. 2004 Mar;10(3):262-7
references.pmid: 14981513
references.citation: Trends Cell Biol. 2010 Nov;20(11):642-9
references.pmid: 20880709
references.citation: Nat Rev Drug Discov. 2009 Aug;8(8):627-44
references.pmid: 19644473
references.citation: Int J Mol Sci. 2012;13(2):2472-80
references.pmid: 22408465
references.citation: Phytomedicine. 2004 Nov;11(7-8):666-72
references.pmid: 15636183
references.citation: Sci Transl Med. 2013 Jan 2;5(166):166ra3
references.pmid: 23283368
references.citation: Oncogene. 2003 Oct 13;22(45):6988-93
references.pmid: 14557802
references.citation: J Biol Chem. 1998 Jul 24;273(30):18984-91
references.pmid: 9668078
references.citation: J Clin Oncol. 1997 Jul;15(7):2564-9
references.pmid: 9215826
references.citation: Cancer Res. 1996 Feb 15;56(4):816-25
references.pmid: 8631019
references.citation: Oncogene. 2008 Sep 18;27(41):5527-41
references.pmid: 18794886
references.citation: Commun Integr Biol. 2009 Sep;2(5):444-7
references.pmid: 19907714
references.citation: Eur J Cell Biol. 2002 Mar;81(3):117-24
references.pmid: 11998863
references.citation: Ann Oncol. 2006 Apr;17(4):553-61
references.pmid: 16303860
references.citation: Biol Cell. 2004 Apr;96(3):215-29
references.pmid: 15182704
references.citation: Ann Oncol. 1994;5 Suppl 6:S3-6
references.pmid: 7865431
references.citation: J Cell Biol. 2005 Aug 15;170(4):571-82
references.pmid: 16103226
references.citation: Oncogene. 2002 Sep 9;21(40):6175-83
references.pmid: 12214247
references.citation: Reprod Sci. 2014 Nov;21(11):1352-61
references.pmid: 24642720
references.citation: Nutr Cancer. 2005;53(2):232-43
references.pmid: 16573384
references.citation: Cancer Chemother Pharmacol. 2012 Sep;70(3):451-9
references.pmid: 22864875
references.citation: J Nat Prod. 2011 Apr 25;74(4):614-9
references.pmid: 21319773
references.citation: Anticancer Res. 2011 May;31(5):1667-76
references.pmid: 21617225
references.citation: J Cell Biol. 2008 Aug 25;182(4):623-9
references.pmid: 18710927
references.citation: Nat Rev Cancer. 2010 May;10(5):342-52
references.pmid: 20414202
references.citation: Biochem Pharmacol. 2015 Mar 1;94(1):1-11
references.pmid: 25562745
references.citation: J Photochem Photobiol B. 2014 Apr 5;133:55-64
references.pmid: 24705371
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Int J Urol. 2007 Nov;14(11):1000-4; discussion 1004
references.pmid: 17956525
references.citation: Nature. 1995 Mar 9;374(6518):131-4
references.pmid: 7877684
references.citation: Food Chem Toxicol. 2014 Mar;65:242-51
references.pmid: 24384411