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Chain elongation analog of resveratrol as potent cancer chemoprevention agent

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Abstract

Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A–C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism.

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Acknowledgments

This work was supported by the Starting Foundation for Doctor of Hebei North University and College Young Talent Program Funding of Hebei Province (BJ2016003).

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Authors and Affiliations

  1. College of Laboratory Medicine, Hebei North University, 11 Diamond Street South, Zhangjiakou, 075000, Hebei Province, People’s Republic of China

    Yan-Fei Kang, Hai-Xia Qiao & Li-Ping Ge

  2. College of Agriculture and Forestry Science and Technology, Hebei North University, Zhangjiakou, 075000, Hebei, China

    Long-Zuo Xin

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  1. Yan-Fei Kang
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  2. Hai-Xia Qiao
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  4. Li-Ping Ge
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Correspondence to Yan-Fei Kang.

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Kang, YF., Qiao, HX., Xin, LZ. et al. Chain elongation analog of resveratrol as potent cancer chemoprevention agent. J Physiol Biochem 72, 445–452 (2016). https://doi.org/10.1007/s13105-016-0487-3

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  • DOI: https://doi.org/10.1007/s13105-016-0487-3

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