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Title: Damnacanthal and its nanoformulation exhibit anti-cancer activity via cyclin D1 down-regulation
Authors: Pakin Sukamporn
Pleumchitt Rojanapanthu
Gabriel Silva
Xiaobo Zhang
Wandee Gritsanapan
Seung Joon Baek
University of Tennessee College of Veterinary Medicine
Mahidol University
Thammasat University
Universidade de Ribeirao Preto
China Pharmaceutical University
Phyto Product Research
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-May-2016
Citation: Life Sciences. Vol.152, (2016), 60-66
Abstract: © 2016 Elsevier Inc. All rights reserved. Aims Damnacanthal is an anthraquinone isolated from the root of Morinda citrifolia L. (noni), and it exhibits many pharmacological properties, including anti-cancer activity. Damnacanthal targets several signal transduction proteins related to cell growth inhibition or apoptosis. However, the molecular mechanisms by which damnacanthal affects cell cycle regulation have not been elucidated in detail. Main methods Cyclin D1 is an important regulatory protein in cell cycle progression and is overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of damnacanthal on cyclin D1 expression. Key findings We found that damnacanthal inhibited growth of several cancer cell lines (HCT-116, HT-29, MCF-7 and PC-3) in a dose- and time-dependent manner with a decrease in cyclin D1 protein expression. Damnacanthal did not change mRNA of cyclin D1; rather it suppressed cyclin D1 expression at the post-translational level. Subsequent experiments with several mutant cyclin D1 constructs suggest that the lysine sites of cyclin D1 play a pivotal role in damnacanthal-mediated cyclin D1 degradation. Furthermore, damnacanthal was encapsulated in self-assembled chitosan nanoparticles to improve both physicochemical and biological activities. Significance Our results suggest that encapsulated damnacanthal exhibits better activity in cell growth inhibition, compared to non-encapsulated damnacanthal. Thus, damnacanthal has potential to be a candidate for the development of chemoprevention or therapeutic agents for cancers.
ISSN: 18790631
Appears in Collections:Scopus 2016-2017

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