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B1, a novel naphthalimide-based DNA intercalator, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation

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Summary

In the course of screening for novel anticancer compounds, B1 (N-(2-(Dimethylamino)ethyl)-2-aminothiazonaphthalimide), a novel naphthalimide-based DNA intercalator, was generated as a new anticancer candidate. For the first time, our investigation demonstrates that B1 inhibited the growth of HeLa cells by the induction of cell cycle arrest and apoptosis. Analysis of flow cytometry and western blots of HeLa cells treated with B1 revealed an appreciable cell cycle arrest and apoptotic induction in dose and time-dependent manner via the p53-dependent pathway. Furthermore, the release of cytochrome c from mitochondria was detected using confocal microscopy in HeLa cells treated with B1. Accordingly, these data demonstrate that the anticancer activity of B1 is associated with the activation of p53 and the release of cytochrome c, which suggest that B1 might have therapeutic potential against cervix carcinoma as an effective lead compound.

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Abbreviations

B1:

N-(2-(Dimethylamino)ethyl)-2-aminothiazonaphthalimide

DMSO:

Dimethyl sulfoxide

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PI:

Propidium iodide

BCIP:

5-bromo-4-chloro-3-indolyl-phosphate

NBT:

Nitro blue tet-razolium

PMSF:

Phenylmethylsulfonyl fluoride

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Acknowledgements

This work was supported by Shanghai Leading Academic Discipline Project, Project No. B507, the National Special Fund for State Key Laboratory of Bioreactor Engineering, Grant No. 2060204 and the 111 Project, Grant No. B07023.

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of Chemical Biology, School of pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Xin Liang, Aibin Wu, Yufang Xu, Ke Xu, Jianwen Liu & Xuhong Qian

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  1. Xin Liang
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  2. Aibin Wu
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  3. Yufang Xu
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  4. Ke Xu
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  5. Jianwen Liu
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  6. Xuhong Qian
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Correspondence to Jianwen Liu or Xuhong Qian.

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Liang, X., Wu, A., Xu, Y. et al. B1, a novel naphthalimide-based DNA intercalator, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation. Invest New Drugs 29, 646–658 (2011). https://doi.org/10.1007/s10637-010-9403-9

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  • DOI: https://doi.org/10.1007/s10637-010-9403-9

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