Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Language

English

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s).

Keywords

Ampelopsis Radix, colorectal cancer, STAT3, apoptosis, migration, invasion

Publication Date

4-2017

Source Publication Title

Frontiers in Pharmacology

Volume

8

Start Page

Article 227

Publisher

Frontiers Media

Peer Reviewed

1

Copyright

© 2017 Su, Bai, Chen, Wang, Fu, Li, Guo, Zhu, Wang and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funder

This work was supported by Science, Technology and Innovation Commission of Shenzhen (JCYJ20140807091945050, JCYJ20150630164505508, and JCYJ20160229210327924); the Research Grants Council of Hong Kong (12125116); the National Natural Science Foundation of China (81673649); Guangdong Natural Science Foundation (2016A030313007), and the Hong Kong Baptist University (FRG1/15-16/050 and FRG2/16-17/033).

DOI

10.3389/fphar.2017.00227

Link to Publisher's Edition

http://dx.doi.org/10.3389/fphar.2017.00227

ISSN (electronic)

16639812

JA-5007-29369_suppl.tif (4115 kB)
FIGURE S1 | High performance liquid chromatography (HPLC) chromatograms of standards and AR. (A)

Additional Files

JA-5007-29369_suppl.tif (4115 kB)
FIGURE S1 | High performance liquid chromatography (HPLC) chromatograms of standards and AR. (A)

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