Nanomolar range docetaxel treatment sensitizes MCF-7 cells to chemotherapy induced apoptosis, induces G2M arrest and phosphorylates bcl-2.
Docetaxel (Taxotere), a member of the taxoid family of chemotherapy drugs is currently being tested in clinical trials simultaneously with other apoptosis inducing drugs like doxorubicin. We show, in vitro, in MCF-7 breast cancer cells that when it is used at doses as low as 5nM, 24 hours before either doxorubicin or etoposide, docetaxel is capable of inducing a significant increase in cell death compared to the reverse sequence or simultaneous treatment. We further show that this increase in cell death is due to an increase in apoptosis, and that this sensitization coincides with a docetaxel induced G2-M arrest and phosphorylation of the bcl-2 oncoprotein. We speculate that this phosphorylation of the apoptosis blocker bcl-2 might be responsible for the sensitization, and we suggest a clinical study comparing a 24 hour docetaxel pretreatment to the current simultaneous schedules.
Berchem
G J
GJ
Laboratoire d'Oncologie Moléculaire, Institut Jules Bordet, Brussels, Belgium. guy_berchem@compuserve.com
Bosseler
M
M
Mine
N
N
Avalosse
B
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D017239:Paclitaxel