Different effect of protein kinase B/Akt and extracellular signal-regulated kinase inhibition on trichostatin A-induced apoptosis in epithelial ovarian carcinoma cell lines

被引:6
|
作者
Jang, Eun-Ra [1 ]
Kim, Yun Jeong [1 ]
Myung, Soon Chul [2 ]
Kim, Wonyong [3 ]
Lee, Chung Soo [1 ]
机构
[1] Chung Ang Univ, Coll Med, Dept Pharmacol, Seoul 156756, South Korea
[2] Chung Ang Univ Hosp, Dept Urol, Seoul 156755, South Korea
[3] Chung Ang Univ, Coll Med, Dept Microbiol, Seoul 156756, South Korea
关键词
Trichostatin A; Akt and ERK inhibitors; Epithelial ovarian adenocarcinoma cell lines; Apoptosis-related proteins; HISTONE DEACETYLASE INHIBITORS; CANCER-CELLS; DEATH; PATHWAY; GROWTH; THERAPY; CLEAVAGE; SURVIVAL; BAX; ACTIVATION;
D O I
10.1007/s11010-011-0768-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Histone deacetylase inhibitor-induced apoptosis in cancer cells may be mediated by the Ras/Raf/MEK/ERK and protein kinase B/Akt signaling pathways. However, inhibition of ERK and Akt activity has different effects on proliferation and apoptosis in cancer cells. We assessed and compared the inhibitory effects of Akt and ERK pathways on the apoptotic effect of trichostatin A using the human epithelial carcinoma cell lines OVCAR-3 and SK-OV-3. Trichostatin A induced nuclear damage, decrease in Bid and Bcl-2 protein levels, increase in Bax levels, cytochrome c release, activation of caspases (8, 9, and 3) and increase in tumor suppressor p53 levels. Akt inhibitor potentiated trichostatin A-induced apoptosis-related protein activation and cell death, whereas ERK inhibitor exhibited an additive toxic effect. These results suggest that the Akt and ERK inhibitors may have a differential effect on trichostatin A-induced apoptosis in human epithelial ovarian carcinoma cell lines. Akt inhibitor may potentiate the apoptotic effect of trichostatin A on ovarian carcinoma cell lines by increasing the activation of the caspase-8-dependent pathway and the mitochondria-mediated cell death pathway, leading to caspase activation. In contrast, ERK inhibitor may exhibit an additive toxic effect on trichostatin A toxicity by increasing apoptosis-related protein activation.
引用
收藏
页码:1 / 11
页数:11
相关论文
共 50 条
  • [21] Protein Kinase B and Extracellular Signal-Regulated Kinase Inactivation is Associated with Regorafenib-Induced Inhibition of Osteosarcoma Progression In Vitro and In Vivo
    Pan, Po-Jung
    Liu, Yu-Chang
    Hsu, Fei-Ting
    JOURNAL OF CLINICAL MEDICINE, 2019, 8 (06)
  • [22] Different effects of amlodipine and enalapril on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase pathway for induction of vascular smooth muscle cell differentiation in vivo
    Umemoto, S
    Kawahara, S
    Hashimoto, R
    Umeji, K
    Matsuda, S
    Tanaka, M
    Kubo, M
    Matsuzaki, M
    HYPERTENSION RESEARCH, 2006, 29 (03) : 179 - 186
  • [23] Decreased phosphorylation of protein kinase B/AKT and extracellular signal-regulated kinase (ERK) in neutrophils from patients with myelodysplasia.
    Fuhler, GM
    Drayer, AL
    Vellenga, E
    BLOOD, 2001, 98 (11) : 291A - 291A
  • [24] Protein Kinase A and B-Raf Mediate Extracellular Signal-Regulated Kinase Activation by Thyrotropin
    Vuchak, Lisa A.
    Tsygankova, Oxana M.
    Prendergast, Gregory V.
    Meinkoth, Judy L.
    MOLECULAR PHARMACOLOGY, 2009, 76 (05) : 1123 - 1129
  • [25] Activation of the Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Pathway Overcomes Cisplatin Resistance in Ovarian Carcinoma Cells
    Nonaka, Michiko
    Itamochi, Hiroaki
    Kawaguchi, Wakae
    Kudoh, Akiko
    Sato, Seiya
    Uegaki, Kazunori
    Naniwa, Jun
    Sato, Shinya
    Shimada, Muneaki
    Oishi, Tetsuro
    Terakawa, Naoki
    Kigawa, Junzo
    Harada, Tasuku
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2012, 22 (06) : 922 - 929
  • [26] Reversal of ultraviolet B-induced immunosuppression by inhibition of the extracellular signal-regulated mitogen-activated protein kinase
    Leng, Hong
    Luo, Xiaoqun
    Ma, Li
    Kang, Kefei
    Zheng, Zhizhong
    PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE, 2009, 25 (05) : 264 - 269
  • [27] Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination
    Ogata, T
    Iijima, S
    Hoshikawa, S
    Miura, T
    Yamamoto, S
    Oda, H
    Nakamura, K
    Tanaka, S
    JOURNAL OF NEUROSCIENCE, 2004, 24 (30): : 6724 - 6732
  • [28] Multiregion Quantification of Extracellular Signal-regulated Kinase Activity in Renal Cell Carcinoma
    Hoerner, Christian R.
    Massoudi, Rustin
    Metzner, Thomas J.
    Stell, Laurel
    O'Rourke, Jennifer J.
    Kong, Christina S.
    Liliental, Joanna E.
    Brooks, James D.
    Sabatti, Chiara
    Leppert, John T.
    Fan, Alice C.
    EUROPEAN UROLOGY ONCOLOGY, 2020, 3 (03): : 360 - 364
  • [29] Inhibition of thrombin-stimulated cell proliferation by ceramide is not through inhibition of extracellular signal-regulated protein kinase
    Guo, YL
    Peng, M
    Kang, BB
    Williamson, JR
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 240 (02) : 405 - 408
  • [30] Involvement of extracellular signal-regulated protein kinase in gliosis induced during recovery from metabolic inhibition
    Masuhara, K
    Ohmichi, M
    Kurachi, H
    Tasaka, K
    Kanzaki, T
    Kimura, A
    Hayakawa, J
    Hisamoto, K
    Koike, K
    Murata, Y
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 267 (03) : 892 - 896