Induction of apoptosis by a potent caffeic acid derivative, caffeic acid undecyl ester, is mediated by mitochondrial damage in NALM-6 human B cell leukemia cells

Tomizawa,Ayako; Kanno,Syu-ichi; Osanai,Yuu; Goto,Akane; Sato,Chizuru; Yomogida,Shin; Ishikawa,Masaaki

doi:10.3892/or.2012.2163

February 2013 Volume 29 Issue 2

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February 2013 Volume 29 Issue 2

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Induction of apoptosis by a potent caffeic acid derivative, caffeic acid undecyl ester, is mediated by mitochondrial damage in NALM-6 human B cell leukemia cells

Authors:
- Ayako Tomizawa
- Syu-ichi Kanno
- Yuu Osanai
- Akane Goto
- Chizuru Sato
- Shin Yomogida
- Masaaki Ishikawa
View Affiliations / Copyright

Affiliations: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai, Japan

Copyright: © Tomizawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 425-429
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Published online on: December 3, 2012

https://doi.org/10.3892/or.2012.2163
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Abstract

Caffeic acid esters have various biological activities, and we previously reported that undecyl caffeate (caffeic acid undecyl ester, CAUE), a new caffeic acid derivative, has strong pharmacological activity. The present study investigated the cytotoxicity of both CAUE and its parent compound, caffeic acid phenethyl ester (CAPE), and characterized the mechanisms by which they induce apoptosis in the human B cell leukemia cell line NALM-6. Treatment with CAUE reduced cell survival in NALM-6 cells but had no significant effect on the survival of normal lymphocytes. When assessing the 50% inhibitory concentration (IC50) for cytotoxicity, CAUE had 10-fold higher activity than CAPE in NALM-6 cells. CAUE treatment resulted in induction of apoptotic features in NALM-6 cells, including cleaved poly (ADP-ribose) polymerase and activated caspase-3. A caspase inhibitor completely blocked CAUE-induced apoptosis. CAUE treatment resulted in a concentration- and time-dependent decrease in both mitochondrial membrane potential and downregulation of Bcl-2 expression. Moreover, CAUE-induced apoptosis was enhanced in the Bcl-2 knockdown condition induced by small interfering RNA. These data suggest that CAUE-induced apoptosis was mediated via an apoptotic intrinsic pathway including mitochondrial damage and was caspase-dependent. These data also suggest that CAUE is a powerful anti-leukemic agent that acts via induction of apoptosis by mitochondrial damage and selective action in leukemia cells.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Induction of apoptosis by a potent caffeic acid derivative, caffeic acid undecyl ester, is mediated by mitochondrial damage in NALM-6 human B cell leukemia cells

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