Details

Autor(en) / Beteiligte

• Song, Xue-Qing
• Ma, Zhong-Ying
• Wu, Yi-Gang
• Dai, Miao-Liang
• Wang, Dong-Bo
• Xu, Jing-Yuan
• Liu, Yangzhong

Titel

New NSAID-Pt(IV) prodrugs to suppress metastasis and invasion of tumor cells and enhance anti-tumor effect in vitro and in vivo

Ist Teil von

• European journal of medicinal chemistry, 2019-04, Vol.167, p.377-387

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The great interest in epithelial-to-mesenchymal transition (EMT) programme lies in its association with process of metastasis and invasion, which is a crucial cause of cancer-related death. Herein, we designed and reported three new NSAID-Pt(IV) prodrugs, taking Non-Steroid Anti-Inflammatory Drugs (NSAIDs) to disrupt EMT programme and assist genotoxic platinum-based drugs as a cytotoxicity booster, to offer a class of potential anticarcinogens with a multi-functional action mechanism. The NSAID-Pt(IV) prodrugs, especially Eto-Pt(IV), highly enhanced cellular uptake with amount up to 42-fold at 3 h compared with CDDP, and greatly increased DNA damage and cell apoptosis, showing much higher cytotoxicity than cisplatin in the tested cancer cells even in A549/cis cells. Among of them, Eto-Pt(IV) and Car-Pt(IV) exhibited more excellent activity than Sul-Pt(IV), arising from their reduction-labile and favorable lipophilicity. Most strikingly, Eto-Pt(IV) markedly inhibited metastasis and invasion of MCF-7 cells, owing to its COX-2 suppression that down-regulated active MMP-2, vimentin protein and up-regulated E-cadherin. In vivo, Eto-Pt(IV) displayed potent antitumor activity and no observable toxicity in BALB/c nude mice bearing MCF-7 tumors. [Display omitted] •NSAID-Pt(IV) prodrugs displayed potent antitumor activity in vitro and in vivo superior to cisplatin.•NSAID-Pt(IV) markedly suppresses tumor cells metastasis and invasion via EMT programme and alleviates drug resistance.•There is no observable toxicity in the test animals.