Inhibiting myosin light chain kinase retards the growth of mammary and prostate cancer cells.
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.
Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, 835 South Wolcott Ave, Chicago, IL 60612-7342, USA.
Lian-Zhi
LZ
Gu
Wen-Yang
WY
Hu
Nenad
N
Antic
Rajendra
R
Mehta
Jerrold R
JR
Turner
Primal
P
de Lanerolle
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology*; D002455:Cell Division; D017024:Chemotherapy, Adjuvant; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D009281:Naphthalenes / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; D001381:Azepines; D009281:Naphthalenes; C070571:ML 7; D005047:Etoposide; D009219:Myosin-Light-Chain Kinase