Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus

Guochuan Sun, Zongping Zheng, Mee Hyun Lee, Yijuan Xu, Soouk Kang, Zigang Dong, Mingfu Wang, Zhennan Gu, Haitao Li, Wei Chen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

Original languageEnglish (US)
Pages (from-to)3474-3480
Number of pages7
JournalJournal of agricultural and food chemistry
Volume65
Issue number17
DOIs
StatePublished - May 3 2017

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (81402366, 31530056 National Youth 1000 Talents Plan), Jiangsu Specially Appointed Professor and the Fundamental Research Funds for the Central Universities (JUSRP11549 and JUSRP51501).

Publisher Copyright:
© 2017 American Chemical Society.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Akt
  • Artocarpus heterophyllus
  • artocarpin
  • colorectal cancer

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