Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways.

Gloria Bonuccelli,Federica Sotgia,Michael P Lisanti

doi:10.18632/aging.101483

Abstract

Matcha green tea (MGT) is a natural product that is currently used as a dietary supplement and may have significant anti-cancer properties. However, the molecular mechanism(s) underpinning its potential health benefits remain largely unknown. Here, we used MCF7 cells (an ER(+) human breast cancer cell line) as a model system, to systematically dissect the effects of MGT at the cellular level, via i) metabolic phenotyping and ii) unbiased proteomics analysis. Our results indicate that MGT is indeed sufficient to inhibit the propagation of breast cancer stem cells (CSCs), with an IC-50 of ~0.2 mg/ml, in tissue culture. Interestingly, metabolic phenotyping revealed that treatment with MGT is sufficient to suppress both oxidative mitochondrial metabolism (OXPHOS) and glycolytic flux, shifting cancer cells towards a more quiescent metabolic state. Unbiased label-free proteomics analysis identified the specific mitochondrial proteins and glycolytic enzymes that were down-regulated by MGT treatment. Moreover, to discover the underlying signalling pathways involved in this metabolic shift, we subjected our proteomics data sets to bio-informatics interrogation via Ingenuity Pathway Analysis (IPA) software. Our results indicate that MGT strongly affected mTOR signalling, specifically down-regulating many components of the 40S ribosome. This raises the intriguing possibility that MGT can be used as inhibitor of mTOR, instead of chemical compounds, such as rapamycin. In addition, other key pathways were affected, including the anti-oxidant response, cell cycle regulation, as well as interleukin signalling. Our results are consistent with the idea that MGT may have significant therapeutic potential, by mediating the metabolic reprogramming of cancer cells.

Highlights

Breast cancer is a leading cause of women’s cancers, a small fraction of men may be affected [1]
Matcha green tea (MGT) treatment inhibited the sphere-formation capacity of MCF7 cells by 50%, indicating that MGT halts the propagation of cancer stem cells (Fig. 1B)
MGT treated cells displayed a reduction of glycolytic rate and glycolytic capacity, the latter referred to as measurement of the maximal capacity of the cells to respond to a higher ATP demand (Fig. 3)

Summary

Introduction

Breast cancer is a leading cause of women’s cancers, a small fraction of men may be affected [1]. In this context, tumor recurrence [2] is lethal and in the advanced stages is associated with treatment failure, due to therapy resistance [3, 4]. In www.aging‐us.com direct support of this notion, it has been demonstrated that a key component of green tea, namely epigallocatechin-3-gallate, behaves as an anti-oxidant and shows anti-tumor effects against breast cancer cells [7, 8]. Consumption of green tea could partially explain why Asian-American women show a decreased risk for developing breast cancer [11]

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