Siddiqui Imtiaz A, Bharali Dhruba J, Nihal Minakshi, Adhami Vaqar M, Khan Naghma, Chamcheu Jean Christopher, Khan Mohammad Imran, Shabana Sameh, Mousa Shaker A, Mukhtar Hasan
Department of Dermatology, University of Wisconsin-Madison, WI 53706.
The Pharmaceutical Research Institute at Albany, Albany college of Pharmacy and Health Sciences, Albany, NY 12208.
Nanomedicine. 2014 Nov;10(8):1619-26. doi: 10.1016/j.nano.2014.05.007. Epub 2014 Jun 3.
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.
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.
此前我们已证明绿茶多酚表没食子儿茶素-3-没食子酸酯(EGCG)对人黑色素瘤细胞具有抗增殖和促凋亡作用(《国际癌症杂志》。2005年;114(4):513 - 21)。本研究中使用的剂量在生理上无法达到,且对于化学预防而言,首选的给药途径是口服。为克服这些缺点,并利用我们的纳米化学预防新概念(《癌症研究》。2009年;69(5):1712 - 6),我们开发了一种基于纳米技术的口服给药系统来封装EGCG。在此,使用人黑色素瘤Mel 928细胞,我们证明这种纳米制剂相对于天然EGCG具有8倍的剂量优势。此外,经纳米EGCG处理的细胞显示出明显的凋亡诱导和细胞周期抑制,以及Mel 928肿瘤异种移植的生长。纳米EGCG还抑制了从处理过的小鼠身上收获的肿瘤中的增殖(Ki - 67和PCNA)并诱导了凋亡(Bax、PARP)。这些观察结果促使在强大的人黑色素瘤动物模型中对纳米EGCG进行进一步的体内疗效研究。
该研究团队开发了一种基于纳米技术的口服给药系统,将一种源自绿茶的多酚EGCG封装在壳聚糖纳米颗粒中。使用人黑色素瘤细胞,证明其相对于天然EGCG具有8倍的剂量优势,导致可测量的凋亡诱导和增殖抑制,这值得进一步进行体内研究。