Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and exhibits tumoricidal activity in vivo.
The transcription inhibitor tetra-O-methyl nordihydroguaiaretic acid (M4N) was found to arrest the proliferation of C3, C33a, CEM-T4, and TC-1 cells in culture at the G2 stage of the cell cycle. Investigation into the mechanism of arrest revealed that M4N reduces mRNA levels and subsequent protein production of the cyclin-dependent kinase CDC2, resulting in the inactivation of the CDC2/cyclin B complex (maturation promoting factor). When injected intratumorally in a C3-cell induced C57bl/6 mouse tumor model system, M4N demonstrated substantial tumoricidal activity that correlated with a reduction in tumor cell CDC2 protein levels. These findings suggest that M4N may be a useful chemotherapeutic agent for the control of unregulated cellular proliferation.
Heller
J D
JD
Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Kuo
J
J
Wu
T C
TC
Kast
W M
WM
Huang
R C
RC
D000818:Animals; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D016195:G2 Phase / Q000187:drug effects*; D009637:Masoprocol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C076852:terameprocol; D009637:Masoprocol; D016203:CDC2 Protein Kinase