title: Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells.
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 EGCG-induced 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.
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Kumazoe
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Bae
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takai
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Hidaka
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Shuya
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Yeongseon
authors.initials: Y
authors.lastname: Won
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Tsukamoto
authors.affiliation: Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tachibana
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D021962:Membrane Microdomains / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013662:Tea / Q000737:chemistry
chemical_list: D016588:Anticarcinogenic Agents; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D013108:Sphingomyelin Phosphodiesterase