Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells

Yuhui Huang, Motofumi Kumazoe, Jaehoon Bae, Shuhei Yamada, Mika Takai, Shiori Hidaka, Shuya Yamashita, Yoonhee Kim, Yeongseon Won, Motoki Murata, Shuntaro Tsukamoto, Hirofumi Tachibana

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12 Citations (Scopus)

Abstract

An epidemiological study showed that green tea consumption is associated with a reduced risk of hematopoietic malignancy. The major green tea polyphenol epigallocatechin-3-O-gallate (EGCG) is reported to have anticancer effects. Chronic myeloid leukemia (CML) is a major hematopoietic malignancy characterized by expansion of myeloid cells. In the present study, we showed EGCGinduced acid sphingomyelinase (ASM) activation and lipid raft clustering in CML cells. The ASM inhibitor desipramine significantly reduced EGCG-induced cell death. Protein kinase Cδ is a well-known kinase that plays an important role in ASM activation. We observed EGCG-induced phosphorylation of protein kinase Cδ at Ser664. Importantly, EGCG-induced ASM activation was significantly reduced by pretreatment of CML cells with the soluble guanylate cyclase inhibitor NS2028, suggesting that EGCG induced ASM activation through the cyclic guanosine monophosphate (cGMP)-dependent pathway. Indeed, pharmacological inhibition of a cGMP-negative regulator enhanced the anti-CML effect of EGCG. These results indicate that EGCG-induced cell death via the cGMP/ASM pathway in CML cells.

Original languageEnglish
Pages (from-to)1162-1168
Number of pages7
JournalOncology reports
Volume34
Issue number3
DOIs
Publication statusPublished - Sep 1 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Huang, Y., Kumazoe, M., Bae, J., Yamada, S., Takai, M., Hidaka, S., Yamashita, S., Kim, Y., Won, Y., Murata, M., Tsukamoto, S., & Tachibana, H. (2015). Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells. Oncology reports, 34(3), 1162-1168. https://doi.org/10.3892/or.2015.4086