Cancer signaling: A novel piperazine derivative potently induces caspase-dependent apoptosis…

A novel piperazine derivative potently induces caspase-dependent apoptosis of cancer cells via inhibition of multiple cancer signaling pathways.



She EX, Hao Z. A novel piperazine derivative potently induces caspase-dependent apoptosis of cancer cells via inhibition of multiple cancer signaling pathways. Am J Transl Res 2013 Sep 25;5(6):622-633.



Despite rapid progress in anticancer drug development and improvement in clinical outcomes, the survival rate for many types of cancer is still unacceptably low. Therefore, it is crucial to discover novel anticancer drugs to both prevent and treat the disease. In recent years, the advent of combinatorial chemistry allows the design and parallel synthesis of millions of small compounds that have drug-like properties. In vitro high throughput screening of such compound libraries has allowed the identification of many new drug candidates that may be further evaluated for their efficacy and mechanism of action. The overall objective of this study was to identify small molecule compounds as candidates for anti-cancer drug development. We first used cell proliferation and cytotoxicity assays to identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell line (K562). Six top compounds selected from the initial screening of a library of 2,560 compounds were further evaluated in multiple cancer cell lines to rank the drug candidates. The top candidate was further investigated to elucidate the molecular mechanism underlying its anticancer activity. Our studies suggest that this piperazine derivative effectively (GI50 = 0.06-0.16 μM) inhibits cancer cell proliferation and induces caspase-dependent apoptosis via inhibiting multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases and the BCR-ABL pathways.

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Heather Hopkins

My work explores the relationship between the universality of myth and life as performance.

With influences as diverse as Machiavelli and Joni Mitchell, new combinations are generated from both explicit and implicit meanings.

Ever since I was a teenager I have been fascinated by the essential unreality of the zeitgeist. What starts out as yearning soon becomes corroded into a manifesto of professional courtesy, leaving only a sense of what could have been and the dawn of a new reality.

As momentary replicas become clarified through emergent and repetitive practice, the viewer is left with an epitaph for the outposts of our culture.

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Written by Heather Hopkins

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