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 journalArticle

16 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

Keywords

  • Akt
  • Artocarpus heterophyllus
  • artocarpin
  • colorectal cancer

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    Sun, G., Zheng, Z., Lee, M. H., Xu, Y., Kang, S., Dong, Z., Wang, M., Gu, Z., Li, H., & Chen, W. (2017). Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus. Journal of agricultural and food chemistry, 65(17), 3474-3480. https://doi.org/10.1021/acs.jafc.7b00278