Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells

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• 作者：Terry W. Moody ; Christopher Switzer ; Wilmarie Santana-Flores ; Lisa A. Ridnour ; Marc Berna ; Michelle Thill ; Robert T. Jensen ; Anna Sparatore ; Piero Del Soldato ; Grace C. Yeh ; David D. Roberts ; Giuseppe
• 关键词：S-valproate ; S-diclofenac ; Lung cancer ; PGE₂ ; E-cadherin
• 刊名：Lung Cancer
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：68
• 期：2
• 页码：154-160
• 全文大小：753 K

文摘

The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 μg/ml concentrations significantly reduced prostaglandin (PG)E₂ levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 μg/ml, respectively. Using the MTT assay, 10 μg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18 mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE₂ levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC.