Deguelin, a natural rotenoid, inhibits mouse myeloma cell growth in vitro via induction of apoptosis

被引:8
作者
Li, Zhengguang [1 ]
Wu, Jun [1 ]
Wu, Changping [1 ]
Jiang, Jingting [1 ]
Zheng, Xiao [1 ]
Xu, Bin [1 ]
Li, Min [1 ]
机构
[1] Soochow Univ, Dept Oncol, Affiliated Hosp 3, Tianning Zone 213003, Changzhou, Peoples R China
关键词
deguelin; multiple myeloma; apoptosis; CANCER CHEMOPREVENTIVE ACTIVITY; MULTIPLE-MYELOMA; BREAST-CANCER; ORNITHINE-DECARBOXYLASE; ACTIVATED AKT; CYCLE ARREST; EXPRESSION; PHOSPHORYLATION; MITOCHONDRIA; MECHANISM;
D O I
10.3892/ol.2012.790
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Deguelin is a naturally occurring rotenoid with strong cancer chemopreventive and antitumor activities. In the present study, we investigated the antitumor activity of deguelin against MPC-11 murine myeloma cells and the possible mechanism of action in vitro. Our results revealed that deguelin inhibited the proliferation of MPC-11 cells in a concentration- and time-dependent manner and caused the apoptotic death of MPC-11 cells. Following exposure to deguelin, the phosphorylation of Akt was decreased. The inhibition of cell growth may be associated with decreased levels of phosphorylated Akt. Deguelin-induced apoptosis was characterized by the upregulation of Bax, downregulalion of Bcl-2 and activation of caspase-3. In conclusion, deguelin inhibits murine myeloma cell proliferation by inducing apoptosis via regulation of the Bax/Bcl-2 ratio and by inhibition of the activation of Akt. Its potential as an anticancer agent against multiple myeloma warrants further investigation.
引用
收藏
页码:677 / 681
页数:5
相关论文
共 31 条
  • [1] Immunohistochemical localization of phosphorylated AKT in multiple myeloma
    Alkan, S
    Izban, KF
    [J]. BLOOD, 2002, 99 (06) : 2278 - 2279
  • [2] Amundson SA, 2000, CANCER RES, V60, P6101
  • [3] Becker N, 2011, RECENT RESULTS CANC, V183, P25, DOI 10.1007/978-3-540-85772-3_2
  • [4] Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells
    Chun, KH
    Kosmeder, JW
    Sun, SH
    Pezzuto, JM
    Lotan, R
    Hong, WK
    Lee, HY
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (04): : 291 - 302
  • [5] Induction of apoptosis in estrogen receptor-negative breast cancer cells by natural and synthetic cyclopentenones:: Role of the IκB kinase/nuclear factor-κB pathway
    Ciucci, Alessandra
    Gianferretti, Patrizia
    Piva, Roberto
    Guyot, Thierry
    Snape, Timothy J.
    Roberts, Stanley M.
    Santoro, M. Gabriella
    [J]. MOLECULAR PHARMACOLOGY, 2006, 70 (05) : 1812 - 1821
  • [6] Prognostic significance of activated Akt expression in melanoma: A clinicopathologic study of 292 cases
    Dai, DL
    Martinka, M
    Li, G
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (07) : 1473 - 1482
  • [7] Molecular mechanism of apoptosis induction by resveratrol, a natural cancer chemopreventive agent
    Fan, Enguo
    Jiang, Sha
    Zhang, Lijuan
    Bai, Yuhua
    [J]. INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH, 2008, 78 (01) : 3 - 8
  • [8] Anticancer action of cube insecticide:: Correlation for rotenoid constituents between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine decarboxylase activities
    Fang, NB
    Casida, JE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (07) : 3380 - 3384
  • [9] Deguelin inhibits expression of IκBα protein and induces apoptosis of B-CLL cells in vitro
    Geeraerts, B.
    Vanhoecke, B.
    Vanden Berghe, Wim
    Philippe, J.
    Offner, F.
    Deforce, D.
    [J]. LEUKEMIA, 2007, 21 (08) : 1610 - 1618
  • [10] ROTENOIDS MEDIATE POTENT CANCER CHEMOPREVENTIVE ACTIVITY THROUGH TRANSCRIPTIONAL REGULATION OF ORNITHINE DECARBOXYLASE
    GERHAUSER, C
    MAR, W
    LEE, SK
    SUH, N
    LUO, YD
    KOSMEDER, J
    LUYENGI, L
    FONG, HHS
    KINGHORN, AD
    MORIARTY, RM
    MEHTA, RG
    CONSTANTINOU, A
    MOON, RC
    PEZZUTO, JM
    [J]. NATURE MEDICINE, 1995, 1 (03) : 260 - 266