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Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt.

Abstract

Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt signal pathway. Furthermore, BV-induced apoptosis was accompanied by downregulation of Bcl-2, activation of caspase-3 and a subsequent poly(ADP-ribose)polymerase (PARP) cleavages. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (IAP) family proteins. Caspase-3 inhibitor, z-DEVD-fmk, was significantly capable of restoring cell viability and BV-induced apoptosis through caspase-3 activation was significantly attenuated in Bcl-2-overexpressing cells. These results indicate that downregulation of Bcl-2 plays a major role in the initiation as an activator of a caspase-3 involved with BV-induced apoptosis. BV also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. PD98059 (an inhibitor of ERK) or LY294002 (an inhibitor of Akt), but not an inhibitor of p38 MAPK and JNK, significantly decreased cell viability and increased lactate dehydrogenase (LDH) release. The results indicated that key regulators in BV-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of the ERK and Akt signal pathway.

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  • Authors+Show Affiliations

    ,

    Faculty of Applied Marine Science, Cheju National University, Jeju, South Korea.

    , , , , , ,

    Source

    International immunopharmacology 6:12 2006 Dec 05 pg 1796-807

    MeSH

    Animals
    Apoptosis
    Bee Venoms
    Bone Marrow Cells
    Caspase 3
    Cell Proliferation
    Cell Survival
    Collagen Type XI
    DNA Fragmentation
    Down-Regulation
    Extracellular Signal-Regulated MAP Kinases
    HL-60 Cells
    Humans
    K562 Cells
    L-Lactate Dehydrogenase
    Mice
    Mice, Inbred C57BL
    Proto-Oncogene Proteins c-akt
    Proto-Oncogene Proteins c-bcl-2
    U937 Cells

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17052670

    Citation

    Moon, Dong-Oh, et al. "Key Regulators in Bee Venom-induced Apoptosis Are Bcl-2 and Caspase-3 in Human Leukemic U937 Cells Through Downregulation of ERK and Akt." International Immunopharmacology, vol. 6, no. 12, 2006, pp. 1796-807.
    Moon DO, Park SY, Heo MS, et al. Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. Int Immunopharmacol. 2006;6(12):1796-807.
    Moon, D. O., Park, S. Y., Heo, M. S., Kim, K. C., Park, C., Ko, W. S., ... Kim, G. Y. (2006). Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. International Immunopharmacology, 6(12), pp. 1796-807.
    Moon DO, et al. Key Regulators in Bee Venom-induced Apoptosis Are Bcl-2 and Caspase-3 in Human Leukemic U937 Cells Through Downregulation of ERK and Akt. Int Immunopharmacol. 2006 Dec 5;6(12):1796-807. PubMed PMID: 17052670.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. AU - Moon,Dong-Oh, AU - Park,Sung-Yong, AU - Heo,Moon-Soo, AU - Kim,Ki-Cheon, AU - Park,Cheol, AU - Ko,Woo Shin, AU - Choi,Yung Hyun, AU - Kim,Gi-Young, Y1 - 2006/08/22/ PY - 2006/06/27/received PY - 2006/07/21/revised PY - 2006/07/25/accepted PY - 2006/10/21/pubmed PY - 2007/1/11/medline PY - 2006/10/21/entrez SP - 1796 EP - 807 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 6 IS - 12 N2 - Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt signal pathway. Furthermore, BV-induced apoptosis was accompanied by downregulation of Bcl-2, activation of caspase-3 and a subsequent poly(ADP-ribose)polymerase (PARP) cleavages. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (IAP) family proteins. Caspase-3 inhibitor, z-DEVD-fmk, was significantly capable of restoring cell viability and BV-induced apoptosis through caspase-3 activation was significantly attenuated in Bcl-2-overexpressing cells. These results indicate that downregulation of Bcl-2 plays a major role in the initiation as an activator of a caspase-3 involved with BV-induced apoptosis. BV also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. PD98059 (an inhibitor of ERK) or LY294002 (an inhibitor of Akt), but not an inhibitor of p38 MAPK and JNK, significantly decreased cell viability and increased lactate dehydrogenase (LDH) release. The results indicated that key regulators in BV-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of the ERK and Akt signal pathway. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/17052670/Key_regulators_in_bee_venom_induced_apoptosis_are_Bcl_2_and_caspase_3_in_human_leukemic_U937_cells_through_downregulation_of_ERK_and_Akt_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(06)00230-X DB - PRIME DP - Unbound Medicine ER -