Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

Abstract

(–)-Epigallocatechin-3-gallate (EGCG), the major bioactive constituent in green tea, has been reported to effectively inhibit the formation and development of tumors. To maximize the effectiveness of EGCG, we attached it to nanogold particles (EGCG-pNG) in various ratios to examine in vitro cytotoxicity and in vivo anti-cancer activity. EGCG-pNG showed improved anti-cancer efficacy in B16F10 murine melanoma cells; the cytotoxic effect in the melanoma cells treated with EGCG-pNG was 4.91 times higher than those treated with EGCG. The enhancement is achieved through mitochondrial pathway-mediated apoptosis as determined by annexin V assay, JC-10 staining, and caspase-3, -8, -9 activity assay. Moreover, EGCG-pNG was 1.66 times more potent than EGCG for inhibition of tumor growth in a murine melanoma model. In the hemolysis assay, the pNG surface conjugated with EGCG is most likely the key factor that contributes to the decreased release of hemoglobin from human red blood cells.

Green tea polyphenols and their potential role in health and disease

“…A preventive role of EGCG in cardiotoxicity induced by DOX has been reported (Li et al 2010). In addition, EGCG plays a dose-dependent inhibitory role in autophagy signaling and inhibits the cellular growth with a synergistic effect (40-60 % increment) on cell death when combined with doxorubicin (Chen et al 2014a). This is further confirmed by a combination therapy with rapamycin, an autophagy antagonist which impairs the anticancer effect of either DOX by itself or in combination with EGCG (Chen et al 2014a).…”

“…EGCG also has the ability to sensitize the efficacy of numerous chemotherapy agents such as doxorubicin (DOX) and chrysin in hepatic carcinoma, gastric cancer, etc. (Chen et al 2014a;Sun et al 2011). A preventive role of EGCG in cardiotoxicity induced by DOX has been reported (Li et al 2010).…”

“…In addition, EGCG plays a dose-dependent inhibitory role in autophagy signaling and inhibits the cellular growth with a synergistic effect (40-60 % increment) on cell death when combined with doxorubicin (Chen et al 2014a). This is further confirmed by a combination therapy with rapamycin, an autophagy antagonist which impairs the anticancer effect of either DOX by itself or in combination with EGCG (Chen et al 2014a). DOX encapsulated in 6-O-(3-hexadecyloxy-2-hydroxypropyl)-hyaluronic acid nanoparticles, 9HDHA-NPs, with EGCG significantly inhibits the growth of Ehrlich ascites tumors (Ray et al 2013).…”

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

“…A summary of the studies using different EGCG nanocarriers for cancer management and carried out in cell lines and in animals is depicted in Table 1. Gold NPs as EGCG delivery systems have been exploited in several types of cancer since gold has anti-cancer properties per se [85,100]. Several reports have described the in vitro and in vivo efficacy of gold NPs in conjugation with EGCG for cancer treatment, including for the bladder, melanoma, neuroblastoma, and hepatocarcinoma [84][85][86][87].…”

ImprovingIn VivoEfficacy of Bioactive Molecules: An Overview of Potentially Antitumor Phytochemicals and Currently Available Lipid-Based Delivery Systems

“… Table 6 shows and overviews the lipid and nonlipid formulations specifically designed to parenteral and topical Phy administration. In case of the parenteral route, most of the investigations have focused on utilizing carriers to enhance antitumor efficiency through passive targeting or active targeting [153, 154], controlling drug release at the tumor site to minimize side effects [155, 156], or overcoming multidrug resistance [157]. Parenteral nanocarriers include either lipid formulations (liposomes, SLNs, and NCLs) or polymer formulations (polymeric NPs and polymer-bioactive conjugates).…”