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

Int J Mol Med. 2020 Sep;46(3):1085-1095. doi: 10.3892/ijmm.2020.4665. Epub 2020 Jul 2.

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.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cadherins / genetics*
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Isothiocyanates / pharmacology*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / prevention & control
  • Sulfoxides / pharmacology*
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology

Substances

  • Anticarcinogenic Agents
  • Cadherins
  • FAT1 protein, human
  • Isothiocyanates
  • Sulfoxides
  • sulforaphane