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Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway

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Abstract

Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

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Acknowledgements

This study was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (No. 2011-0030074, No. 2010-0009582).

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Authors and Affiliations

  1. Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women’s University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea

    Guang-zhi Dong, Ji Hye Jeong, Yu-ih Lee, So Yoon Lee, Hui-Yuan Zhao, Raok Jeon & Jae-Ha Ryu

  2. Department of Natural Medicine Resources, Semyung University, 65 Semyung-Ro, Jecheon, Chungbuk, 390-711, Republic of Korea

    Hwa Jin Lee

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  1. Guang-zhi Dong
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Dong, Gz., Jeong, J.H., Lee, Yi. et al. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway. Arch. Pharm. Res. 40, 509–517 (2017). https://doi.org/10.1007/s12272-017-0905-2

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