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

• Published in: Nanomedicine 2014-11, Vol.10 (8), p.1619-1626
• Main Authors: Siddiqui, Imtiaz A., PhD, Bharali, Dhruba J., PhD, Nihal, Minakshi, PhD, Adhami, Vaqar M., PhD, Khan, Naghma, PhD, Chamcheu, Jean Christopher, PhD, Khan, Mohammad Imran, PhD, Shabana, Sameh, PhD, Mousa, Shaker A., PhD, Mukhtar, Hasan, PhD
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Catechin - therapeutic use; Cell Line, Tumor; Cell Proliferation - drug effects; Chitosan; Chitosan - chemistry; EGCG; Humans; Internal Medicine; Male; Melanoma; Melanoma - drug therapy; Mice; Mice, Nude; Nanoparticles - chemistry; Nanotechnology; Nanotechnology - methods; Xenograft Model Antitumor Assays
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2014.05.007

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. From the Clinical Editor 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.