Sulforaphane suppresses the viability and metastasis, and promotes the apoptosis of bladder cancer cells by inhibiting the expression of FAT‑1 Corrigendum in /10.3892/ijmm.2022.5149

Wang,Fei; Liu,Penghua; An,Hexiang; Zhang,Yu

doi:10.3892/ijmm.2020.4665

Sulforaphane suppresses the viability and metastasis, and promotes the apoptosis of bladder cancer cells by inhibiting the expression of FAT‑1

Corrigendum in: /10.3892/ijmm.2022.5149

Authors:
- Fei Wang
- Penghua Liu
- Hexiang An
- Yu Zhang
View Affiliations

Affiliations: Shenzhen Key Laboratory of Viral Oncology, Clinical Innovation and Research Center, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong 518101, P.R. China, Department of Urology, Baoan Central Hospital of Shenzhen, The Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518102, P.R. China
Published online on: July 2, 2020 https://doi.org/10.3892/ijmm.2020.4665
Pages: 1085-1095
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

FAT atypical cadherin 1 (FAT1) regulates complex mechanisms for the promotion of oncogenesis or the suppression of malignancies. Sulforaphane (SFN) has antioxidant and anti‑tumor activities. The present study investigated the roles of SFN and FAT1 in bladder cancer (BC). The expression of FAT1 in BC cell lines and tissues was measured by western blot analysis and reverse transcription‑quantitative PCR (RT‑qPCR). The association between FAT1 expression and the 5‑year survival rate of patients with BC was evaluated. The viability of and FAT1 expression in T24 and SW780 cells exposed to various concentrations of SFN were detected by MTT assay, and western blot analysis and RT‑qPCR, respectively. Furthermore, the viability, migration, invasion and apoptosis of and FAT1 expression in BC cells subjected to FAT1 overexpression or knockdown, and with or without SFN stimulation, were examined. The results revealed that FAT1 expression in BC cells and tissues was increased, and patients with a high FAT‑1 expression had a shorter 5‑year survival time than those with a low FAT‑1 expression. BC cell viability and FAT1 expression were suppressed by SFN in a concentration‑dependent manner. The knockdown of FAT1 inhibited the viability, migration and invasion, and promoted the apoptosis of BC cells, whereas the overexpression of FAT1 produced opposite effects. In addition, cells exposed to SFN exhibited a reduced viability, migration, invasion and an increased apoptosis, effects which were promoted by FAT1 knockdown; however, the overexpression of FAT1 blocked the above‑mentioned effects of SFN on the cells. On the whole, the present study demonstrates that SFN suppresses the progression of BC by inhibiting the expression of FAT‑1; thus, SFN may be used as a potential drug for the treatment of BC.

View Figures

View References

1	Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A and Bray F: Bladder cancer incidence and mortality: A global overview and recent trends. Eur Urol. 71:96–108. 2017. View Article : Google Scholar
2	Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, Hinoue T, Laird PW, Hoadley KA, Akbani R, et al: comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 171:540–556.e25. 2017. View Article : Google Scholar : PubMed/NCBI
3	Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström PU, Choi W, Guo CC, Lotan Y and Kassouf W: Bladder cancer. Lancet. 388:2796–2810. 2016. View Article : Google Scholar : PubMed/NCBI
4	Ebrahimi H, Amini E, Pishgar F, Moghaddam SS, Nabavizadeh B, Rostamabadi Y, Aminorroaya A, Fitzmaurice C, Farzadfar F, Nowroozi MR, et al: Global, regional and national burden of bladder cancer, 1990 to 2016: Results from the GBD study 2016. J Urol. 201:893–901. 2019. View Article : Google Scholar : PubMed/NCBI
5	Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C, Chen Q, Tan Y, Cui T, Zheng Y and Cai L: Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 57:82–95. 2013. View Article : Google Scholar : PubMed/NCBI
6	Wang G, Nie JH, Bao Y and Yang X: Sulforaphane rescues ethanol-suppressed angiogenesis through oxidative and endoplasmic reticulum stress in chick embryos. J Agric Food Chem. 66:9522–9533. 2018. View Article : Google Scholar : PubMed/NCBI
7	Liu P, Atkinson SJ, Akbareian SE, Zhou Z, Munsterberg A, Robinson SD and Bao Y: Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. Sci Rep. 7:126512017. View Article : Google Scholar
8	Russo M, Spagnuolo C, Russo GL, Skalicka-Woźniak K, Daglia M, Sobarzo-Sánchez E, Nabavi SF and Nabavi SM: Nrf2 targeting by sulforaphane: A potential therapy for cancer treatment. Crit Rev Food Sci Nutr. 58:1391–1405. 2018. View Article : Google Scholar
9	McMahon M, Itoh K, Yamamoto M and Hayes JD: Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem. 278:21592–21600. 2003. View Article : Google Scholar : PubMed/NCBI
10	Jeong WS, Keum YS, Chen C, Jain MR, Shen G, Kim JH, Li W and Kong AN: Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J Biochem Mol Biol. 38:167–176. 2005.PubMed/NCBI
11	Choi S and Singh SV: Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent. Cancer Res. 65:2035–2043. 2005. View Article : Google Scholar : PubMed/NCBI
12	Yeh CT and Yen GC: Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells. Carcinogenesis. 26:2138–2148. 2005. View Article : Google Scholar : PubMed/NCBI
13	Hu R, Kim BR, Chen C, Hebbar V and Kong AN: The roles of JNK and apoptotic signaling pathways in PEITC-mediated responses in human HT-29 colon adenocarcinoma cells. Carcinogenesis. 24:1361–1367. 2003. View Article : Google Scholar : PubMed/NCBI
14	Liu ZM, Chen GG, Ng EK, Leung WK, Sung JJ and Chung SC: Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells. Oncogene. 23:503–513. 2004. View Article : Google Scholar
15	Gamet-Payrastre L, Lumeau S, Gasc N, Cassar G, Rollin P and Tulliez J: Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs. 9:141–148. 1998. View Article : Google Scholar : PubMed/NCBI
16	Islam SS, Mokhtari RB, Akbari P, Hatina J, Yeger H and Farhat WA: Simultaneous targeting of bladder tumor growth, survival, and epithelial-to-mesenchymal transition with a novel therapeutic combination of acetazolamide (AZ) and sulforaphane (SFN). Target Onco. 11:209–227. 2016. View Article : Google Scholar
17	Jo GH, Kim GY, Kim WJ, Park KY and Choi YH: Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway. Int J Oncol. 45:1497–1506. 2014. View Article : Google Scholar : PubMed/NCBI
18	Park HS, Han MH, Kim GY, Moon SK, Kim WJ, Hwang HJ, Park KY and Choi YH: Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells. Food Chem Toxicol. 64:157–165. 2014. View Article : Google Scholar
19	Wang S, Zhao X, Yang S, Chen B and Shi J: Salidroside alleviates high glucose-induced oxidative stress and extracellular matrix accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3 inflammasome pathway. Chem Biol Interact. 278:48–53. 2017. View Article : Google Scholar : PubMed/NCBI
20	Srivastava C, Irshad K, Dikshit B, Chattopadhyay P, Sarkar C, Gupta DK, Sinha S and Chosdol K: FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma. Int J Cancer. 142:805–812. 2018. View Article : Google Scholar
21	Hu X, Zhai Y, Shi R, Qian Y, Cui H, Yang J, Bi Y, Yan T, Yang J, Ma Y, et al: FAT1 inhibits cell migration and invasion by affecting cellular mechanical properties in esophageal squamous cell carcinoma. Oncol Rep. 39:2136–2146. 2018.PubMed/NCBI
22	Dikshit B, Irshad K, Madan E, Aggarwal N, Sarkar C, Chandra PS, Gupta DK, Chattopadhyay P, Sinha S and Chosdol K: FAT1 acts as an upstream regulator of oncogenic and inflammatory pathways, via PDCD4, in glioma cells. Oncogene. 32:3798–3808. 2013. View Article : Google Scholar
23	Cazier JB, Rao SR, McLean CM, Walker AK, Wright BJ, Jaeger EE, Kartsonaki C, Marsden L, Yau C, Camps C, et al: Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden. Nat Commun. 5:37562014. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	Ranjit M, Motomura K, Ohka F, Wakabayashi T and Natsume A: Applicable advances in the molecular pathology of glioblastoma. Brain Tumor Pathol. 32:153–162. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kan SF, Wang J and Sun GX: Sulforaphane regulates apoptosis- and proliferation-related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer. Int J Mol Med. 42:2447–2458. 2018.PubMed/NCBI
27	Choi YH: ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells. Gen Physiol Biophys. 37:129–140. 2018. View Article : Google Scholar : PubMed/NCBI
28	Wang DX, Zou YJ, Zhuang XB, Chen SX, Lin Y, Li WL, Lin JJ and In ZQ: Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways. Acta Pharmacol Sin. 38:241–251. 2017. View Article : Google Scholar
29	Lin SC, Lin LH, Yu SY, Kao SY, Chang KW, Cheng HW and Liu CJ: FAT1 somatic mutations in head and neck carcinoma are associated with tumor progression and survival. Carcinogenesis. 39:1320–1330. 2018.PubMed/NCBI
30	Hayes TF, Benaich N, Goldie SJ, Sipilä K, Ames-Draycott A, Cai W, Yin G and Watt FM: Integrative genomic and functional analysis of human oral squamous cell carcinoma cell lines reveals synergistic effects of FAT1 and CASP8 inactivation. Cancer Lett. 383:106–114. 2016. View Article : Google Scholar : PubMed/NCBI
31	Pileri P, Campagnoli S, Grandi A, Parri M, De Camilli E, Song C, Ganfini L, Lacombe A, Naldi I, Sarmientos P, et al: FAT1: A potential target for monoclonal antibody therapy in colon cancer. Br J Cancer. 115:40–51. 2016. View Article : Google Scholar : PubMed/NCBI
32	Kranz D and Boutros M: A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis. EMBO J. 33:181–197. 2014.PubMed/NCBI
33	Shan Y, Zhang L, Bao Y, Li B, He C, Gao M, Feng X, Xu W, Zhang X and Wang S: Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells. J Nutr Biochem. 24:1062–1069. 2013. View Article : Google Scholar
34	Ahmed AF, de Bock CE, Sontag E, Hondermarck H, Lincz LF and Thorne RF: FAT1 cadherin controls neuritogenesis during NTera2 cell differentiation. Biochem Biophys Res Commun. 514:625–631. 2019. View Article : Google Scholar : PubMed/NCBI
35	Martin D, Degese MS, Vitale-Cross L, Iglesias-Bartolome R, Valera JLC, Wang Z, Feng X, Yeerna H, Vadmal V, Moroishi T, et al: Assembly and activation of the Hippo signalome by FAT1 tumor suppressor. Nat Commun. 9:23722018. View Article : Google Scholar : PubMed/NCBI
36	Alamoud KA and Kukuruzinska MA: Emerging insights into Wnt/β-catenin signaling in head and neck cancer. J Dent Res. 97:665–673. 2018. View Article : Google Scholar : PubMed/NCBI
37	Hu X, Zhai Y, Kong P, Cui H, Yan T, Yang J, Qian Y, Ma Y, Wang F, Li H, et al: FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer. Cancer Lett. 397:83–93. 2017. View Article : Google Scholar : PubMed/NCBI
38	Grifantini R, Taranta M, Gherardini L, Naldi I, Parri M, Grandi A, Giannetti A, Tombelli S, Lucarini G, Ricotti L, et al: Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer. J Control Release. 280:76–86. 2018. View Article : Google Scholar : PubMed/NCBI
39	Zhang Z, Li C, Shang L, Zhang Y, Zou R, Zhan Y and Bi B: Sulforaphane induces apoptosis and inhibits invasion in U251MG glioblastoma cells. Springerplus. 5:2352016. View Article : Google Scholar : PubMed/NCBI