Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

被引:32
作者
Almeida, Tamires Cunha [1 ]
Coelho Guerra, Camila Chaves [2 ]
Goncalves De Assis, Barbara Leticia [1 ]
de Oliveira Aguiar Soares, Rodrigo Dian [3 ]
Garcia, Camila Carriao Machado [2 ,4 ]
Lima, Angelica Alves [1 ,5 ]
da Silva, Glenda Nicioli [1 ,4 ,5 ]
机构
[1] Univ Fed Ouro Preto, Programa Posgrad Ciencias Farmaceut CIPHARMA, Ouro Preto, MG, Brazil
[2] Univ Fed Ouro Preto, Inst Ciencias Exatas & Biol, Dept Ciencias Biol DECBI, Ouro Preto, MG, Brazil
[3] Univ Fed Ouro Preto, Lab Multiusuario Citometria Fluxo, Ouro Preto, MG, Brazil
[4] Univ Fed Ouro Preto, Programa Posgrad Ciencias Biol CBIOL, Ouro Preto, MG, Brazil
[5] Univ Fed Ouro Preto, Escola Farm, Dept Anal Clin DEACL, Ouro Preto, MG, Brazil
关键词
bladder cancer; resveratrol; TP53; gene; TUMOR-SUPPRESSOR GENE; DNA-DAMAGE; P53; MUTATIONS; MEDIATED APOPTOSIS; NUCLEAR ANTIGEN; IN-VITRO; CYCLE; EXPRESSION; NECROSIS; LINES;
D O I
10.1002/em.22297
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 mu M) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. (c) 2019 Wiley Periodicals, Inc.
引用
收藏
页码:740 / 751
页数:12
相关论文
共 57 条
  • [1] Antigenotoxic effects of resveratrol: assessment of in vitro and in vivo response
    Abraham, Suresh K.
    Khandelwal, Nidhi
    Hintzsche, Henning
    Stopper, Helga
    [J]. MUTAGENESIS, 2016, 31 (01) : 27 - 33
  • [2] Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications
    Alarcn de la Lastral, C.
    Villegas, I.
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 2007, 35 : 1156 - 1160
  • [3] Immunohistochemical study of cyclooxygenase-2 in skin tumors
    Amirnia, Mehdi
    Babaie-ghazani, Arash
    Fakhrjou, Ashraf
    Khodaeiani, Effat
    Alikhah, Hossein
    Naghavi-behzad, Mohammad
    Zarrintan, Armin
    [J]. JOURNAL OF DERMATOLOGICAL TREATMENT, 2014, 25 (05) : 380 - 387
  • [4] [Anonymous], SCI REP
  • [5] Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends
    Antoni, Sebastien
    Ferlay, Jacques
    Soerjomataram, Isabelle
    Znaor, Ariana
    Jemal, Ahmedin
    Bray, Freddie
    [J]. EUROPEAN UROLOGY, 2017, 71 (01) : 96 - 108
  • [6] Resveratrol-Cu(II) induced DNA breakage in human peripheral lymphocytes: Implications for anticancer properties
    Azmi, AS
    Bhat, SH
    Hadi, SM
    [J]. FEBS LETTERS, 2005, 579 (14): : 3131 - 3135
  • [7] Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells
    Bai, Yu
    Yang, Hong
    Zhangi, Guoying
    Hu, Libing
    Lei, Yonghong
    Qin, Yang
    Yang, Yong
    Wang, Qilin
    Li, Ruiqian
    Mao, Qiqi
    [J]. MOLECULAR MEDICINE REPORTS, 2017, 15 (02) : 885 - 889
  • [8] Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo
    Bai, Yu
    Mao, Qi-Qi
    Qin, Jie
    Zheng, Xiang-Yi
    Wang, Yun-Bin
    Yang, Kai
    Shen, Hua-Feng
    Xie, Li-Ping
    [J]. CANCER SCIENCE, 2010, 101 (02) : 488 - 493
  • [9] DNA hypermethylation in tumorigenesis - epigenetics joins genetics
    Baylin, SB
    Herman, JG
    [J]. TRENDS IN GENETICS, 2000, 16 (04) : 168 - 174
  • [10] In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors
    Brassesco, Maria Sol
    Pezuk, Julia Alejandra
    Morales, Andressa Gois
    de Oliveira, Jaqueline Carvalho
    Roberto, Gabriela Molinari
    da Silva, Glenda Nicioli
    de Oliveira, Harley Francisco
    Scrideli, Carlos Alberto
    Tone, Luiz Gonzaga
    [J]. CANCER BIOLOGY & THERAPY, 2013, 14 (07) : 648 - 657