Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer.

Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer. Research Abstract Details 

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Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer. Abstract Text:

Jinhai Fan,Jennifer Stanfield,Yi Guo,Jose A Karam,Eugene Frenkel,Xiankai Sun,Jer-Tsong Hsieh,

PURPOSE: Romidepsin (FK228, depsipeptide, FR901228), a unique cyclic depsipeptide with a histone deacetylase inhibitor (HDACI) activity, is a potential cancer therapeutic agent and currently under clinical trials for several types of cancer. For bladder cancer, romidepsin seems to be a potent antitumor agent from our recent study. In this study, we further delineate a new agent that can enhance both HDACI and antitumor activity of romidepsin. EXPERIMENTAL DESIGN: We screened a chemical library to identify candidate(s) that could enhance romidepsin activity. Chemical synthesis and purification were carried out to produce pure compound to examine its biochemical and antitumor effect on bladder cancer cell lines both in vitro and in vivo. RESULTS: Tranilast, N-(acetoacetyl) anthranilic acid, was first identified as a lead compound from screening, and then, one of the analogues, 2,3-dimethoxycinnamoyl azide (DMCA), seems to be more potent than tranilast. Our data indicate that DMCA can potentiate the HDACI activity of romidepsin and other biological activities, such as cell cycle arrest and apoptosis; these effects were accompanied with the expression of various key cell cycle regulators in different bladder cancer cells. Consistently, DMCA can enhance the in vivo antitumor effect of romidepsin without causing any more weight loss than romidepsin alone. CONCLUSION: DMCA is able to enhance the antitumor effect of romidepsin on bladder cancer from in vitro and in vivo.

Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer. Publishing Authors By Initials

J Fan,J Stanfield,Y Guo,JA Karam,E Frenkel,X Sun,JT Hsieh,

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Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 14

Page Numbers: 1200-7

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Feb

YEAR: 2008

Effect of trans-2,3-dimethoxycinnamoyl azide on enhancing antitumor activity of romidepsin on human bladder cancer. Information

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LANGUAGE: eng

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AFFILIATION: Authors' Affiliations: Departments of Urology, Radiology, and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas and Department of Urology, The First Hospital of Xi'an Jiaotong University, Xi'an, China.

Country: United States

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MEDLINETA: Clin Cancer Res

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