Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol

Hung-Yun Lin, Dominique Delmas, Ole Vang, Tze-Chen Hsieh, Sharon Lin , Guei-Yun Cheng, Hsiao-Ling Chiang , Chiao En Chen , Heng-Yuan Tang, Dana Crawford, Jacqueline Whang-Peng, Jaulang Hwang, Leroy Liu, Joseph Wu

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.
    OriginalsprogEngelsk
    TidsskriftJournal of Cellular Biochemistry
    Vol/bind114
    Udgave nummer8
    Sider (fra-til)1940-1954
    ISSN0730-2312
    DOI
    StatusUdgivet - 2013

    Emneord

    • ceramide
    • resveratrol
    • COX-2
    • p53
    • p38 kinase
    • apoptosis

    Citer dette

    Lin, Hung-Yun ; Delmas, Dominique ; Vang, Ole ; Hsieh, Tze-Chen ; Lin , Sharon ; Cheng, Guei-Yun ; Chiang , Hsiao-Ling ; Chen , Chiao En ; Tang, Heng-Yuan ; Crawford, Dana ; Whang-Peng, Jacqueline ; Hwang, Jaulang ; Liu, Leroy ; Wu, Joseph. / Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol. I: Journal of Cellular Biochemistry. 2013 ; Bind 114, Nr. 8. s. 1940-1954.
    @article{1079dc8b8b3c4d02aebda5f6b8a3b454,
    title = "Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol",
    abstract = "Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.",
    keywords = "ceramide, resveratrol, COX-2, p53, p38 kinase, apoptosis, ceramide, resveratrol, COX-2, p53, p38 kinase, apoptosis",
    author = "Hung-Yun Lin and Dominique Delmas and Ole Vang and Tze-Chen Hsieh and Sharon Lin and Guei-Yun Cheng and Hsiao-Ling Chiang and Chen, {Chiao En} and Heng-Yuan Tang and Dana Crawford and Jacqueline Whang-Peng and Jaulang Hwang and Leroy Liu and Joseph Wu",
    year = "2013",
    doi = "10.1002/jcb.24539",
    language = "English",
    volume = "114",
    pages = "1940--1954",
    journal = "Journal of Cellular Biochemistry",
    issn = "0730-2312",
    publisher = "JohnWiley & Sons, Inc.",
    number = "8",

    }

    Lin, H-Y, Delmas, D, Vang, O, Hsieh, T-C, Lin , S, Cheng, G-Y, Chiang , H-L, Chen , CE, Tang, H-Y, Crawford, D, Whang-Peng, J, Hwang, J, Liu, L & Wu, J 2013, 'Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol', Journal of Cellular Biochemistry, bind 114, nr. 8, s. 1940-1954. https://doi.org/10.1002/jcb.24539

    Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol. / Lin, Hung-Yun; Delmas, Dominique; Vang, Ole; Hsieh, Tze-Chen; Lin , Sharon; Cheng, Guei-Yun; Chiang , Hsiao-Ling; Chen , Chiao En; Tang, Heng-Yuan; Crawford, Dana; Whang-Peng, Jacqueline; Hwang, Jaulang; Liu, Leroy; Wu, Joseph.

    I: Journal of Cellular Biochemistry, Bind 114, Nr. 8, 2013, s. 1940-1954.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol

    AU - Lin, Hung-Yun

    AU - Delmas, Dominique

    AU - Vang, Ole

    AU - Hsieh, Tze-Chen

    AU - Lin , Sharon

    AU - Cheng, Guei-Yun

    AU - Chiang , Hsiao-Ling

    AU - Chen , Chiao En

    AU - Tang, Heng-Yuan

    AU - Crawford, Dana

    AU - Whang-Peng, Jacqueline

    AU - Hwang, Jaulang

    AU - Liu, Leroy

    AU - Wu, Joseph

    PY - 2013

    Y1 - 2013

    N2 - Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.

    AB - Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.

    KW - ceramide

    KW - resveratrol

    KW - COX-2

    KW - p53

    KW - p38 kinase

    KW - apoptosis

    KW - ceramide

    KW - resveratrol

    KW - COX-2

    KW - p53

    KW - p38 kinase

    KW - apoptosis

    U2 - 10.1002/jcb.24539

    DO - 10.1002/jcb.24539

    M3 - Journal article

    VL - 114

    SP - 1940

    EP - 1954

    JO - Journal of Cellular Biochemistry

    JF - Journal of Cellular Biochemistry

    SN - 0730-2312

    IS - 8

    ER -