Benzyl isothiocyanate (BITC) induces apoptosis in ovarian cancer cells in vitro

J Exp Ther Oncol. 2006;5(4):287-300.


Advanced ovarian cancer (OC) is not curable by surgery alone and chemotherapy is essential for its treatment. Isothiocyanates have been shown to inhibit carcinogen-induced tumorigenesis in animal models, yet no efforts have been made to determine their therapeutic potential in OC. In the present study, we investigated the mechanism of the anti-proliferative and apoptotic activity of benzyl isothiocyanate (BITC) in OC. BITC inhibited the proliferation of OC cells and induced apoptosis in OC cells. Apoptosis was induced by a strong activation of caspase-3 and -9, and cleavage of PARP-1. However, caspase-8 was not activated by BITC. Cytotoxic effects of BITC were reversed by the inhibition caspase-3 and -9 specific inhibitors. BITC showed a concentration dependent decrease in the levels of Bcl-2 with a concomitant increase in Bax levels. In addition, BITC activated proapoptotic signaling by phosphorylation JNK1/2 and p38 while simultaneously inhibiting survival signaling mediated by ERK1/2 and Akt phosphorylation in a dose-dependent manner. While JNK inhibitor SP600125 and p38 inhibitor SB203580, abolished the cytotoxic effect of BITC, MEK inhibitor, PD98059 and PI3 kinase inhibitor, LY294002 failed to show such reversal indicating a critical role played by JNK1/2 and p38 signaling in apoptosis induced by BITC. In summary, our studies demonstrate that BITC inhibits proliferation of OC cells and induces apoptosis via caspase-9 and -3 pathways. BITC inhibits ERK1/2 and Akt survival signaling while simultaneously activating pro-apoptotic p38 and JNK1/2. Therefore, BITC can be potentially developed as a therapeutic agent to treat OC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • DNA Replication / drug effects
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Female
  • HL-60 Cells
  • Humans
  • Isothiocyanates / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Isothiocyanates
  • Proto-Oncogene Proteins c-bcl-2
  • benzyl isothiocyanate
  • Caspase 3
  • Caspase 9