Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth.
The effects of lipoxygenase inhibitors were investigated using human lung cancer cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of NSCLC cell lines tested with IC50 values of 3, 2, and 7 microM, respectively. Using a clonogenic assay, 10 microM NDGA significantly reduced NSCLC colony number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the tumors were excised and analyzed, nude mice treated with NDGA had significantly more apoptotic figures than did untreated tumors. A/J mice treated with urethane developed adenomas after 4 months and NDGA administration significantly reduced lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit lung cancer growth and prevent lung carcinogenesis.
Moody
T W
TW
Cell and Cancer Biology Department, National Cancer Institute, Rockville, Maryland, USA. moodyt@bprb.nci.nih.gov
Leyton
J
J
Martinez
A
A
Hong
S
S
Malkinson
A
A
Mulshine
J L
JL
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007211:Indoles / Q000494:pharmacology; D008084:Lipoxygenase / Q000235:genetics; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D017931:DNA Primers; D004273:DNA, Neoplasm; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; D012333:RNA, Messenger; C078266:MK 0591; D009637:Masoprocol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D008084:Lipoxygenase