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Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein

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Abstract

The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer.

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Authors and Affiliations

  1. Department of Emergency, Xinqiao Hospital, Chongqing, 400037, China

    Ren-Jie Zhou

  2. Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Daping, Yuzhong District, Chongqing, 400042, People’s Republic of China

    Xue-Qin Yang, Dong Wang, Qian Zhou, Lei Xia, Meng-Xia Li, Lin-Li Zeng, Ge Wang & Zhen-Zhou Yang

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  1. Ren-Jie Zhou
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  2. Xue-Qin Yang
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  3. Dong Wang
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  4. Qian Zhou
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  5. Lei Xia
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  6. Meng-Xia Li
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  7. Lin-Li Zeng
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  8. Ge Wang
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  9. Zhen-Zhou Yang
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Correspondence to Zhen-Zhou Yang.

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Ren-Jie Zhou and Xue-Qin Yang contributed equally to this work.

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Zhou, RJ., Yang, XQ., Wang, D. et al. Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein. Cell Biochem Biophys 62, 177–184 (2012). https://doi.org/10.1007/s12013-011-9279-0

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  • DOI: https://doi.org/10.1007/s12013-011-9279-0

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