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Inactivation of HDAC3 and STAT3 is Critically Involved in 1-Stearoyl-sn-Glycero-3-Phosphocholine-Induced Apoptosis in Chronic Myelogenous Leukemia K562 Cells

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Abstract

We here investigated the anticancer mechanism of 1-stearoyl-sn-glycero-3-phosphocholine (LPC), one of the lysophosphatidylcholines, in chronic myelogenous leukemia (CML) K562 cells. LPC significantly showed cytotoxicity at 80 μM and induced apoptosis by sub-G1 accumulation, increase in Annexin V positive and caspase activation. LPC enhanced histone H3 acetylation but decreased histone deacetylase (HDAC) activity and HDAC3 expression. LPC also inhibited phosphorylation of STAT3, its DNA binding activity and nuclear co-localization of HDAC3 and STAT3. In addition, LPC effectively attenuated the expression of survival genes such as Cyclin D1, Cyclin E, Bcl-xL, Bcl-2 and survivin but did not affect COX-2 expression in K562 cells. Furthermore, LPC suppressed phosphorylation of Src and Janus activated kinase 2 while promoted the expression of tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1). Consistently, silencing SHP-1 and pervanadate, an inhibitor of protein tyrosine phosphatase, reversed inactivation of HDAC and STAT3, cleavages of caspase 3 and poly (ADP-ribose) polymerase in LPC-induced apoptosis. Of note, chromatin immunoprecipitation assay revealed that LPC suppressed the binding of HDAC3 and STAT3 to Bcl-xL, Bcl-2 and survivin promoter. Overall, our findings indicate that inactivation of STAT3 and HDAC mediates LPC-induced apoptosis in CML K562 cells.

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Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2012-0005755).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, South Korea

    Ji Hoon Jung, Soo-Jin Jeong, Ji-Hyun Kim, Sung-Ki Jung, Deok-Beom Jung, Duckgu Lee, Eun Jung Sohn, Miyong Yun, Hyo-Jung Lee, Hyo-Jeong Lee & Sung-Hoon Kim

  2. Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, Daejeon, South Korea

    Soo-Jin Jeong

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  1. Ji Hoon Jung
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Correspondence to Sung-Hoon Kim.

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Ji Hoon Jung and Soo-Jin Jeong contributed equally to this work.

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Jung, J.H., Jeong, SJ., Kim, JH. et al. Inactivation of HDAC3 and STAT3 is Critically Involved in 1-Stearoyl-sn-Glycero-3-Phosphocholine-Induced Apoptosis in Chronic Myelogenous Leukemia K562 Cells. Cell Biochem Biophys 67, 1379–1389 (2013). https://doi.org/10.1007/s12013-013-9670-0

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