tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo.
tetra-O-methylnordihydroguaiaretic acid is a derivative of a naturally-occurring lignan, nordihydroguaiaretic acid, that has previously been shown to inhibit various cancer types in vitro and in vivo. Additionally, nordihydroguaiaretic acid has been shown to have nephrotoxic effects in the rat. Here we show that tetra-O-methylnordihydroguaiaretic acid inhibits the growth of a number of tumor cell lines in vitro by inducing apoptosis in a non-schedule-dependent manner. Further, this compound inhibits the synthesis of DNA by melanoma cells and causes cell cycle arrest in G0/G1 and G2/M phases of the cell cycle. tetra-O-Methylnordihydroguaiaretic acid also inhibits the growth of both murine and human melanomas and human colon cancer in vivo without apparent hepatic or renal toxicity.
Lambert
J D
JD
Arizona Cancer Center, The University of Arizona, P.O. Box 245024, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA.
Meyers
R O
RO
Timmermann
B N
BN
Dorr
R T
RT
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D007425:Intracellular Membranes / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D009637:Masoprocol / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000633:toxicity; D008545:Melanoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; C076852:terameprocol; D009637:Masoprocol