title: Damnacanthal and its nanoformulation exhibit anti-cancer activity via cyclin D1 down-regulation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA; Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Pakin
authors.initials: P
authors.lastname: Sukamporn
authors.affiliation: Drug Discovery and Development Center, Thammasat University, Pathumthani 12121, Thailand.
authors.forename: Pleumchitt
authors.initials: P
authors.lastname: Rojanapanthu
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA; Biotechnology Unit, University of Ribeirão Preto, Ribeirão Preto 14096-900, SP, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Silva
authors.affiliation: Department of Physiology, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Phyto Product Research, Bangkok 10800, Thailand.
authors.forename: Wandee
authors.initials: W
authors.lastname: Gritsanapan
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA. Electronic address: sbaek2@utk.edu.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan; D019938:Cyclin D1 / Q000096:biosynthesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004339:Drug Compounding; D005079:Excipients; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D032066:Morinda / Q000737:chemistry; D053758:Nanoparticles; D011499:Protein Processing, Post-Translational
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D019938:Cyclin D1; C079170:damnacanthal; D048271:Chitosan
keywords: Chitosan; Cyclin D1; Damnacanthal; Noni