Sulforaphane Inhibits the Proliferation of the BIU87 Bladder Cancer Cell Line via IGFBP-3 Elevation

  • Published : 2014.02.28


Aim: To investigate effects of sulforaphane on the BIU87 cell line and underlying mechanisms involving IGFBP-3. Methods: Both BIU87 and IGFBP-3-silenced BIU87 cells were treated with sulforaphane. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were determined via flow cytometry. Quantitative polymerase chain reaction and Western blotting were applied to analyze the expression of IGFBP-3 and NF-${\kappa}B$ at both mRNA and protein levels. Results: Sulforaphane (80 ${\mu}M$) treatment could inhibit cell proliferation, inducing apoptosis and cell cycle arrest at G2/M phase. All these effects could be antagonized by IGFBP-3 silencing. Furthermore, sulforaphane (80 ${\mu}M$) could down-regulate NF-${\kappa}B$ expression while elevating that of IGFBP-3. Conclusions: Sulforaphane could suppress the proliferation of BIU87 cells via enhancing IGFBP-3 expression, which negatively regulating the NF-${\kappa}B$ signaling pathway.


  1. Shen G, Xu C, Chen C, et al (2006). p53-independent G1 cell cycle arrest of human colon carcinoma cells HT-29 bysulforaphane is associated with induction of p21CIP1 and inhibition of expression of cyclin D1. Cancer Chemother Pharmacol, 57, 317-27.
  2. Kleszczynski K, Ernst IM, Wagner AE, et al (2013). Sulforaphaneand phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes.Pharmacol Res, 78, 28-40.
  3. Lee YC, Jogie-Brahim S, Lee DY, et al (2011). Insulin-likegrowth factor-binding protein-3 (IGFBP-3) blocks the effectsof asthma by negatively regulating NF-kappaB signalingthrough IGFBP-3R-mediated activation of caspases. J Biol Chem, 286, 17898-909.
  4. Montgomery JS, Miller DC, Weizer AZ, et al (2013). Quality indicators in the management of bladder cancer. J Natl Compr Canc Netw, 11, 492-500.
  5. Wang M, Chen S, Wang S, et al (2012). Effects of phytochemicalssulforaphane on uridine diphosphate-glucuronosyltransferaseexpression as well as cell-cycle arrest and apoptosis in humancolon cancer Caco-2 cells. Chin J Physiol, 55, 134-44.
  6. Wang Z, Liang Z, Liu J, et al (2013). Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer. Onco Targets Ther, 6, 1437-44.
  7. Williams AC, Smartt H, H-Zadeh AM, et al (2007). Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. Cell Death Differ,14, 137-45.
  8. Zhang GJ, Zhang Z (2013). Effect of Bcl-2 on apoptosis and transcription factor NF-kappaB activation induced byadriamycin in bladder carcinoma BIU87 cells. Asian Pac J Cancer Prev, 14, 2387-91.
  9. Herman-Antosiewicz A, Xiao H, Lew KL, et al (2007). Inductionof p21 protein protects against sulforaphane-induced mitoticarrest in LNCaP human prostate cancer cell line. Mol Cancer Ther, 6, 1673-81.
  10. Ferreira U, Matheus WE, Nardi Pedro R, et al (2007). Primary invasive versus progressive invasive transitional cell bladdercancer: multicentric study of overall survival rate.Urol Int, 79, 200-3
  11. Frydoonfar HR, McGrath DR, Spigelman AD (2004).Sulforaphane inhibits growth of a colon cancer cell line.Colorectal Dis, 6, 28-31.
  12. Ge WQ, Pu JX, Zheng SY (2012). Clinical application of the adenosine triphosphate-based response assay in intravesicalchemotherapy for superficial bladder cancer. Asian Pac J Cancer Prev, 13, 689-92.
  13. Johnston N (2004). Sulforaphane halts breast cancer cell growth.Drug Discov Today, 9, 908.
  14. Kalluri HS, Dempsey RJ (2011). IGFBP-3 inhibits theproliferation of neural progenitor cells. Neurochem Res,36, 406-11.
  15. Adams JM, Cory S (1998). The Bcl-2 protein family: arbiters of cell survival. Science, 281, 1322-6.
  16. Butt AJ, Williams AC, (2001). IGFBP-3 and apoptosis--a licenseto kill? Apoptosis, 6, 199-205.
  17. Kim HS, Lee WJ, Lee SW, et al (2010). Insulin-like growth factorbinding protein-3 induces G1 cell cycle arrest with inhibitionof cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells. Horm Metab Res, 42, 165-72.
  18. Kim MR, Zhou L, Park BH, et al., (2011). Induction of G (2)/M arrest and apoptosis by sulforaphane in human osteosarcomaU2-OS cells. Mol Med Rep, 4, 929-34.
  19. Chang CC, Hung CM, Yang YR, et al (2013). Sulforaphaneinduced cell cycle arrest in the G2/M phase via the blockade of cyclin B1/CDC2 in human ovarian cancer cells. J Ovarian Res, 6, 41.
  20. Chen X, Liu J, Chen SY, (2013). Sulforaphane protects against ethanol-induced oxidative stress and apoptosis in neuralcrest cells by the induction of Nrf2-mediated antioxidant response. Br J Pharmacol, 169, 437-48.
  21. Dolcet X, Llobet D, Pallares J, et al (2005). NF-kB in development and progression of human cancer. Virchows Arch, 446, 475-82.
  22. Fang Y, Sun H, Zhai J, et al (2011). Antitumor activity of NF-kB decoy oligodeoxynucleotides in a prostate cancer cell line. Asian Pac J Cancer Prev, 12, 2721-6.

Cited by

  1. Expression and Underlying Roles of IGFBP-3 in Paclitaxel-Treated Gastric Cancer Sgc-7901 Cells vol.15, pp.14, 2014,
  2. Sulforaphane (SFN): An Isothiocyanate in a Cancer Chemoprevention Paradigm vol.2, pp.3, 2015,
  3. Wogonoside induces apoptosis in Bel-7402, a hepatocellular carcinoma cell line, by regulating Bax/Bcl-2 pp.1792-1082, 2015,
  4. Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention vol.62, pp.18, 2018,