title: Excellent anti-proliferative and pro-apoptotic effects of (-)-epigallocatechin-3-gallate encapsulated in chitosan nanoparticles on human melanoma cell growth both in vitro and in vivo.
abstract: Earlier we demonstrated the anti-proliferative and pro-apoptotic effects of green tea polyphenol epigallocatechin-3-gallate (EGCG) on human melanoma cells (Int J Cancer. 2005; 114(4): 513-21). The doses used in this study were not physiologically attainable and for chemoprevention the preferred route of administration is oral consumption. To overcome these shortcomings, and taking advantage of our novel concept of nanochemoprevention (Cancer Res. 2009;69(5):1712-6), we developed a nanotechnology based oral delivery system to encapsulate EGCG. Here, using human melanoma Mel 928 cells we demonstrate 8-fold dose advantage of this nanoformulation over native EGCG. Further, nano-EGCG treated cells showed marked induction of apoptosis and cell cycle inhibition along with the growth of Mel 928 tumor xenograft. Nano-EGCG also inhibited proliferation (Ki-67 and PCNA) and induced apoptosis (Bax, PARP) in tumors harvested from the treated mice. These observations warrant further in vivo efficacy studies of nano-EGCG in robust animal models of human melanoma.
  
  
  BACKGROUND
  This team of investigators developed a nanotechnology based oral delivery system to encapsulate EGCG, a green tea-derived polyphenol in chitosan nanoparticles. Using human melanoma cells, an eight-fold dose advantage was demonstrated over native EGCG, leading to measurable apoptosis induction and proliferation inhibition, warranting further in vivo investigations.
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Imtiaz A
authors: IA
authors: Siddiqui
authors: The Pharmaceutical Research Institute at Albany, Albany college of Pharmacy and Health Sciences, Albany, NY 12208.
authors: Dhruba J
authors: DJ
authors: Bharali
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Minakshi
authors: M
authors: Nihal
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Vaqar M
authors: VM
authors: Adhami
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Naghma
authors: N
authors: Khan
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Jean Christopher
authors: JC
authors: Chamcheu
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706.
authors: Mohammad Imran
authors: MI
authors: Khan
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706; Department of Zoology, Faculty of science, Mansoura University, Mansoura 35516, Egypt.
authors: Sameh
authors: S
authors: Shabana
authors: The Pharmaceutical Research Institute at Albany, Albany college of Pharmacy and Health Sciences, Albany, NY 12208.
authors: Shaker A
authors: SA
authors: Mousa
authors: Department of Dermatology, University of Wisconsin-Madison, WI 53706. Electronic address: hmukhtar@wisc.edu.
authors: Hasan
authors: H
authors: Mukhtar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D002392:Catechin; D048271:Chitosan; C045651:epigallocatechin gallate
keywords: Chitosan; EGCG; Melanoma; Nanotechnology