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Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells

Oncogene volume 29, pages 4576–4587 (2010)Cite this article

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Abstract

p53 is frequently mutated by genetic alternation or suppressed by various kinds of cellular signaling pathways in human cancers. Recently, we have revealed that p53 is suppressed and eliminated from cells by direct binding with oncogenic K-Ras-induced Snail. On the basis of the fact, we generated specific inhibitors against p53-Snail binding (GN25 and GN29). These chemicals can induce p53 expression and functions in K-Ras-mutated cells. However, it does not show cytotoxic effect on normal cells or K-Ras-wild-type cells. Moreover, GN25 can selectively activate wild-type p53 in p53WT/MT cancer cells. But single allelic mt p53 containing cell line, Panc-1, does not respond to our chemical. In vivo xenograft test also supports the antitumor effect of GN25 in K-Ras-mutated cell lines. These results suggest that our compounds are strong candidate for anticancer drug against K-Ras-initiated human cancers including pancreatic and lung cancers.

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Acknowledgements

This work was supported by national cancer center of Korea (0920250; BJP), by the Bio-Scientific Research Grant funded by the Pusan National University (PNU-2008-101-20080596000; BJP) and by the Priority Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093815; GYS).

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Author notes

  1. S-H Lee, G-N Shen and Y Choi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of molecular Biology, College of Natural Science, Pusan National University, Busan, Republic of Korea

    S-H Lee, Y S Jung, S-J Lee, J-Y Chung & B-J Park

  2. School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea

    S-H Lee, G-N Shen & Y Choi

  3. College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea

    G-N Shen & G Y Song

  4. College of Pharmacy, Pusan National University, Busan, Republic of Korea

    H-S Kim, Y Xu, J-W Lee & N-C Ha

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  1. S-H Lee
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Correspondence to G Y Song or B-J Park.

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Lee, SH., Shen, GN., Jung, Y. et al. Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells. Oncogene 29, 4576–4587 (2010). https://doi.org/10.1038/onc.2010.208

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