Inhibiting myosin light chain kinase retards the growth of mammary and prostate cancer cells

Eur J Cancer. 2006 May;42(7):948-57. doi: 10.1016/j.ejca.2005.12.017. Epub 2006 Mar 30.

Abstract

We have previously shown that ML-7, which inhibits myosin light chain kinase (MLCK), induces apoptosis in transformed and non-transformed cells. We have extended these studies and found that ML-7 stimulates the ability of etoposide to induce apoptosis in Mm5MT mouse mammary adenocarcinoma cells and Mat-Ly-Lu rat prostate cancer cells in vitro. ML-7 was also found to have a chemopreventive effect using an in vitro mouse mammary organ culture model. In vivo experiments demonstrated that ML-7 retards the growth of mammary tumours in mice and prostate tumours in rats. Moreover, ML-7 significantly stimulates the ability of etoposide to prevent the growth of established mammary tumours in mice and prostate tumours in rats. These results provide evidence for the efficacy of ML-7 as an adjuvant to etoposide in these models and warrants further development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology*
  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Azepines / pharmacology*
  • Cell Division
  • Chemotherapy, Adjuvant
  • Etoposide / therapeutic use
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Myosin-Light-Chain Kinase / antagonists & inhibitors*
  • Naphthalenes / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology*
  • Random Allocation
  • Rats

Substances

  • Antineoplastic Agents, Phytogenic
  • Azepines
  • Naphthalenes
  • ML 7
  • Etoposide
  • Myosin-Light-Chain Kinase