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J Agric Food Chem. 2017 May 3;65(17):3474-3480. doi: 10.1021/acs.jafc.7b00278. Epub 2017 Apr 18.

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

Author information

1
School of Food Science and Technology, Jiangnan University , Wuxi 214122, China.
2
The Hormel Institute, University of Minnesota , Austin 55912, United States.
3
School of Biological Sciences, The University of Hong Kong , Hong Kong, China.
4
Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology & Business University , Beijing 100048, China.

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.

KEYWORDS:

Akt; Artocarpus heterophyllus; artocarpin; colorectal cancer

PMID:
28391699
DOI:
10.1021/acs.jafc.7b00278
[Indexed for MEDLINE]

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