Isothiocyanate NB7M causes selective cytotoxicity, pro-apoptotic signalling and cell-cycle regression in ovarian

R K Singh1, T S Lange, K K Kim

  • 1Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Brown University, Providence, RI 02905, USA.

British Journal of Cancer
|November 13, 2008
PubMed

Insights

Indole-3-ethyl isothiocyanate NB7M demonstrates potent, selective cytotoxicity against ovarian cancer cell lines, inducing apoptosis and cell-cycle arrest. This compound shows promise as a potential therapeutic agent for ovarian cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Ovarian cancer remains a leading cause of cancer-related deaths globally.
  • Novel therapeutic agents with selective cytotoxicity are urgently needed.
  • Indole-3-ethyl isothiocyanate NB7M is a compound of interest for its potential anti-cancer properties.

Purpose of the Study:

  • To evaluate the cytotoxic activity of NB7M against various cancer cell lines, with a focus on ovarian cancer.
  • To elucidate the mechanisms underlying NB7M-induced cytotoxicity.
  • To assess the potential of NB7M as a therapeutic drug for ovarian cancer.

Main Methods:

  • In vitro screening of NB7M against a panel of cancer cell lines, including the NCI(60) assay.
  • Detailed mechanistic studies using SKOV-3 ovarian cancer cells.
  • Analysis of apoptosis markers, cell-cycle progression, and signaling pathways.

Main Results:

  • NB7M exhibited potent and selective cytotoxicity against ovarian cancer cell lines (60-70% at 2.5 microM), with higher IC(50) values in control cells.
  • NB7M induced classical hallmarks of apoptosis, including PARP-1 deactivation, caspase activation, and mitochondrial depolarization.
  • Subcytotoxic doses of NB7M inhibited DNA synthesis, caused G1-phase cell-cycle arrest, and modulated key survival and proliferation signaling pathways.

Conclusions:

  • NB7M is a selective cytotoxic agent effective against ovarian cancer cell lines in vitro.
  • NB7M induces apoptosis and suppresses cell growth and proliferation through multiple molecular mechanisms.
  • NB7M warrants further development as a potential therapeutic drug for ovarian cancer.

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