A genomic response of H-358 bronchiolar carcinoma cells to MK 886, an inhibitor of 5-lipoxygenase, assessed with a cDNA array.
Incomplete programmed cell death is one explanation for the escape of cancer cells from therapy. Inhibitors of the enzyme 5-lipoxygenase reduce proliferation and initiate programmed cell death in many different types of malignantly transformed cells. The 5-lipoxygenase inhibitor, MK 886. induces an atypical form of programmed cell death in H-358 bronchiolar lung cancer cells. A genomic response of H-358 cells after 24 hr of culture at a 40 uM concentration that inhibited proliferation was analyzed with a Clontech human cDNA array containing 588 cDNAs corresponding to identified genes. The data grouped into 3 major categories and initial conclusions regarding countervailing, cellular stress, programmed cell death, DNA damage and repair mRNA-responses as possible reasons for escape from the antiproliferative response are discussed. The use of cDNA arrays to estimate the extent to which malignantly transformed cells respond to therapy or why they do not and so infer prognosis and identify possible therapeutic modifications is indicated.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, Il. 60612, USA.
Alrefai
W A
WA
Bonomi
P A
PA
Anderson
C A
CA
Dudeja
P
P
Harris
J E
JE
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects*; D018076:DNA, Complementary / Q000032:analysis*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002722:Chlorobenzenes
D000970:Antineoplastic Agents; D001094:Arachidonate 5-Lipoxygenase; D018076:DNA, Complementary; D007211:Indoles; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes