Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway

Abstract

Epigallocatechin-3-gallate (EGCG), a green tea–derived polyphenol, exhibits antitumor activities. An EGCG nanoemulsion (nano-EGCG) was prepared to improve the stability and reduce the side effects of EGCG for treatment of human lung cancer cells, and the antitumor effects were studied. The possible molecular mechanism underlying its antitumor effects on cultured human lung cancer cells was also elucidated. The antitumor effects of EGCG and nano-EGCG were determined using methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, migration, and invasion assays. In addition, changes in the AMP-activated protein kinase (AMPK) signaling pathway were investigated using Western blot analyses. AMPK inhibitors were used to determine the roles of the AMPK signaling pathway involved in the molecular mechanism of the nano-EGCG. Our results showed that both EGCG and nano-EGCG inhibited the growth of H1299 lung cancer cells, with half-maximal inhibitory concentrations of 36.03 and 4.71 μM, respectively. Additionally, nano-EGCG effectively suppressed lung cancer cell colony formation, migration, and invasion in a dose-dependent manner. Nano-EGCG may inhibit lung cancer cell invasion through matrix metalloproteinase (MMP)-2- and MMP-9-independent mechanisms. Furthermore, the expression of several key regulatory proteins in the AMPK signaling pathway was modulated by nano-EGCG. Nano-EGCG may inhibit lung cancer cell proliferation, colony formation, migration, and invasion through the activation of AMPK signaling pathways. This novel mechanism of nano-EGCG suggests its application in lung cancer prevention and treatment. Our results provide an experimental foundation for further research on its potential activities and effects in vivo.

KDM5B promotes self‐renewal of hepatocellular carcinoma cells through the microRNA‐448–mediated YTHDF3/ITGA6 axis

“…Hence, KDM5B inhibitors or other targeted therapies based on this axis are candidates for experimental treatment of human HCC. Moreover, there is increasing evidence that KDM5B silences the AMPK pathway whereas miR‐448 activates it, 18,29 and that activation of the AMPK pathway inhibits the malignant phenotypes of lung cancer 30 . Therefore, we will focus in future studies on the role of different signalling pathways involved in the promotive effect of KDM5B on HCC through miR‐448–mediated effects on the YTHDF3/ITGA6 axis, aiming to identify new therapeutic targets for treating this disease.…”

Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer

“…Moreover, nano-EGCG efficiently repressed lung cancer cell colony formation, migration, and invasion in a dose-dependent manner. Moreover, Nano-EGCG may inhibit lung cancer cell invasion and inhibit lung cancer cell proliferation, colony formation, migration, and invasion [ 204 ]. Compared with rats fed an aqueous tea polyphenols solution, rats fed the tea polyphenols nanoemulsion had meaningfully lower maximum plasma concentrations (C max ) of EGCG and EGC, whereas area under the plasma concentration-time curve (AUC 0-t ) was increased.…”

Understanding Lung Carcinogenesis from a Morphostatic Perspective: Prevention and Therapeutic Potential of Phytochemicals for Targeting Cancer Stem Cells

“…Combination with quercetin was reported to potentially increase the cellular absorption of EGCG into NSCLC cells [ 131 ]. EGCG is currently presented with the common low oral bioavailability problem; thus, a technique has been developed to improve its concentration in the lung tissue using nanoemulsion [ 132 ].…”