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Genistein-induced apoptosis via Akt signaling pathway in anaplastic large-cell lymphoma

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Abstract

More than half of anaplastic large-cell lymphoma (ALCL) are associated with chromosomal translocation t(2;5)(p23;q35) that leads to the expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncoprotein. NPM-ALK activates the antiapoptotic phosphatidylinositol-3 kinase/Akt (PI3K/Akt) signaling pathway, which plays a critical role in cell survival and apoptosis. Inhibition of the PI3K/Akt pathway has been considered as a therapeutic target for cancer where PI3K/Akt activation is a causative factor. Genistein, a natural isoflavonoid found in soy products, has been shown to inhibit cell growth and induce apoptosis in a wide variety of cell lines. Here, we demonstrated that treatment of two t(2;5) ALCL cell lines, SUDHL-1 and Karpas299, with genistein induced apoptosis in a time- and dose-dependent manner. Concurrently, these cells exhibited a decrease in Akt protein levels and subsequent downregulation of Akt activity (Akt phosphorylation). Furthermore, genistein treatment induced mitochondrial membrane potential change, caspase-3 activation and PARP cleavage. From these results, we conclude that inhibition of the Akt signaling pathway and induction of apoptosis by genistein could be used as a new treatment modality for the prevention and/or treatment of t(2;5) ALCL and other hematopoietic malignancies.

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Abbreviations

ALCL:

Anaplastic large-cell lymphoma

ALK:

Anaplastic lymphoma kinase

NPM:

Nucleophosmin

PARP:

Poly(ADP-ribose) polymerase

PI3K:

Phosphatidylinositol-3 kinase

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Acknowledgements

We sincerely thank Dr. Hitochi Ohno of Kyoto University for providing the SUDHL-1 and Karpas299 cell lines. This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center (TIMRC) of Seoul National University College of Medicine.

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Authors and Affiliations

  1. Department of Pathology and Tumor Immunity, Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-779, Korea

    Sung-Shin Park, Yong-Nyun Kim, Yoon Kyung Jeon, Heejung Kim & Chul Woo Kim

  2. Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea

    Young A Kim & Ji Eun Kim

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  1. Sung-Shin Park
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Correspondence to Chul Woo Kim.

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Sung-Shin Park and Yong-Nyun Kim should be regarded as equal first authors.

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Park, SS., Kim, YN., Jeon, Y.K. et al. Genistein-induced apoptosis via Akt signaling pathway in anaplastic large-cell lymphoma. Cancer Chemother Pharmacol 56, 271–278 (2005). https://doi.org/10.1007/s00280-004-0974-z

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