Inhibition of arachidonic acid metabolism decreases tumor cell invasion and matrix metalloproteinase expression.
Head and neck cancers are known to synthesize arachidonic acid metabolites. Interfering with arachidonic acid metabolism may inhibit growth and invasiveness of cancer cells. In this study we investigate effects of sulindac (the non-selective COX inhibitor), aspirin (the irreversible, preferential COX-1 inhibitor), NS-398 (the selective COX-2 inhibitor), NDGA (nordihydroguaiaretic acid, the selective LOX inhibitor) and ETYA (5,8,11,14-eicosatetraynoic acid, the COX and LOX inhibitor) on cell viability, MMP-2 and MMP-9 activities, and in vitro invasion of cancer cells derived from primary and metastatic head and neck, and colon cancers. The inhibitors of COX and/or LOX could inhibit cell proliferation, MMP activity and invasion in head and neck and colon cancer cells. However, the inhibitory effect was obviously observed in colon cancer cells. Inhibition of arachidonic acid metabolism caused a decrease in cancer cell motility, which partially explained by the inhibition of MMPs. Therefore, COX and LOX pathways play important roles in head and neck cancer cell growth.
Koontongkaew
Sittichai
S
Oral Biology Laboratory, Faculty of Dentistry, Thammasat University, Praholyothin Road, Klong Luang, Pratum-Tani 12120, Thailand. koontongkaew@yahoo.com
Monthanapisut
Paopanga
P
Saensuk
Theeranuch
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases