Oncotarget

Research Papers:

Griffipavixanthone, a dimeric xanthone extracted from edible plants, inhibits tumor metastasis and proliferation via downregulation of the RAF pathway in esophageal cancer

Zhijie Ding, Yuanzhi Lao, Hong Zhang, Wenwei Fu, Lunlun Zhu, Hongsheng Tan and Hongxi Xu _

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Oncotarget. 2016; 7:1826-1837. https://doi.org/10.18632/oncotarget.6484

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Abstract

Zhijie Ding1,2,*, Yuanzhi Lao1,2,*, Hong Zhang1,2, Wenwei Fu1,2, Lunlun Zhu1,2, Hongsheng Tan1,2, Hongxi Xu1,2

1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China

2Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Hongxi Xu, e-mail: xuhongxi88@gmail.com

Keywords: Griffipavixanthone, RAF, esophageal cancer, metastasis, natural product

Received: June 28, 2015     Accepted: November 16, 2015     Published: December 07, 2015

ABSTRACT

Metastasis causes a large number of deaths among esophageal cancer patients. The activation of RAF family proteins elevates tumor metastasis and proliferation. In screen targeting the RAF protein, we identified that Griffipavixanthone (GPX), a dimeric xanthone isolated from Garcinia esculenta, is a B-RAF and C-RAF inhibitor against esophageal cancer cells. Using wound healing, transwell migration and matrigel invasion assays, we confirmed that GPX significantly inhibited cell migration and invasion. Furthermore, exposure to GPX rendered cell proliferation and induced G2/M cell cycle arrest. Our mechanistic study showed that GPX suppressed cancer metastasis and proliferation through downregulation of RAF-MEK-ERK cascades proteins as well as RAF mRNA levels. In a pulmonary metastasis model, the intraperitoneal injection of GPX significantly suppressed esophageal tumor metastasis and ERK protein level in vivo. In conclusion, our present study suggested that GPX could inhibit tumor migration, invasion and proliferation in vitro and in vivo, which indicated the potential of GPX for preventing and treating esophageal cancer.


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