Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways

  • Authors:
    • Chin-Chung Lin
    • Chao-Lin Kuo
    • Mau-Hwa Lee
    • Kuang-Chi Lai
    • Jing-Pin Lin
    • Jai-Sing Yang
    • Chun-Shu Yu
    • Chi-Cheng Lu
    • Jo-Hua Chiang
    • Fu-Shin Chueh
    • Jing-Gung Chung
  • View Affiliations

  • Published online on: May 3, 2011     https://doi.org/10.3892/ijo.2011.1027
  • Pages: 217-224
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Abstract

Wogonin (5,7-dihydroxy-8-methoxyflavone) is a flavone constituent of Scutellaria baicalensis with various beneficial biological activities and it has been shown to have tumor therapeutic potential in vitro and in vivo. The purpose of this study was to investigate the effects of wogonin in a human osteosarcoma cell line (U-2 OS). Results showed that a dose- and time-dependent reduction occurred in cell viability after exposure to wogonin in U-2 OS cells. Increasing the levels of reactive oxygen species (ROS) and Ca2+ but decreasing the levels of mitochondrial membrane potential (∆Ψm) were examined in wogonin-treated U-2 OS cells. Flow cytometric assay indicated that wogonin induced sub-G1 phase (apoptosis) and increased caspase-3 activity in examined cells. Wogonin-induced apoptosis in U-2 OS cells was also confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining. Also, results from Western blotting indicated that wogonin increased the levels of Bad, Bax, cytochrome c, cleaved caspase-9, cleaved caspase-3, AIF, Endo G, Fas/CD95, caspase-8, GADD153, GRP78, ATF-6α, calpain 1, calpain 2 and caspase-4 then leading to cell apoptosis. In conclusion, wogonin induced ROS production and intracellular Ca2+, and altered the levels of anti- (Bcl-2) and pro- (Bad and Bax) apoptotic proteins. Wogonin-induced apoptosis in U-2 OS cells was through the activation of caspase-3. In conclusion, these are the first findings to show wogonin-induced cytotoxic effects through induction of apoptotic cell death and ER stress in U-2 OS cells. The potent in vitro antitumor activities suggest that wogonin could be developed for the treatment of human osteosarcoma in the future.

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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lin C, Kuo C, Lee M, Lai K, Lin J, Yang J, Yu C, Lu C, Chiang J, Chueh F, Chueh F, et al: Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways. Int J Oncol 39: 217-224, 2011
APA
Lin, C., Kuo, C., Lee, M., Lai, K., Lin, J., Yang, J. ... Chung, J. (2011). Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways. International Journal of Oncology, 39, 217-224. https://doi.org/10.3892/ijo.2011.1027
MLA
Lin, C., Kuo, C., Lee, M., Lai, K., Lin, J., Yang, J., Yu, C., Lu, C., Chiang, J., Chueh, F., Chung, J."Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways". International Journal of Oncology 39.1 (2011): 217-224.
Chicago
Lin, C., Kuo, C., Lee, M., Lai, K., Lin, J., Yang, J., Yu, C., Lu, C., Chiang, J., Chueh, F., Chung, J."Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways". International Journal of Oncology 39, no. 1 (2011): 217-224. https://doi.org/10.3892/ijo.2011.1027