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Published Online: 4 December 2012

Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells In Vitro and In Vivo via the Regulation of Mitogen-Activated Protein Kinase Pathways

Publication: Cancer Biotherapy and Radiopharmaceuticals
Volume 27, Issue Number 10

Abstract

To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.

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Information & Authors

Information

Published In

cover image Cancer Biotherapy and Radiopharmaceuticals
Cancer Biotherapy and Radiopharmaceuticals
Volume 27Issue Number 10December 2012
Pages: 701 - 710
PubMed: 22849560

History

Published online: 4 December 2012
Published in print: December 2012
Published ahead of print: 31 July 2012

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    Authors

    Affiliations

    Cheng-zhen Liang
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Xin Zhang
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Hao Li
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Yi-qing Tao
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Li-jiang Tao
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Zi-ru Yang
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Xiao-peng Zhou
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
    Zhong-li Shi
    Institute of Orthopedic Research, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
    Hui-min Tao
    Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

    Notes

    Address correspondence to: Hui-min Tao; Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine,Zhejiang University; #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China
    E-mail: [email protected]

    Disclosure Statement

    No competing financial interests exist.

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