Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway



Anti-Cancer Agents in Medicinal Chemistry, 12(5): 554-563.

Author(s): Chengzhen Liang, Hao Li, Chengchun Shen, Jianbo Lai, Zhongli Shi, Bing Liu and Hui-min Tao.

Affiliation: Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, China.

Abstract

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.

Keywords:

Akt, Apoptosis, Gemcitabine, Genistein, NF-κB, Osteosarcoma, Immunoblotting, Electron Microscopy, Xenograft, Electrophoretic, Immunohistochemistry.



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Article Details

Volume: 12
Issue Number: 5
First Page: 554
Last Page: 563
Page Count: 10
DOI: 10.2174/187152012800617867
Price: $58
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