Cocoa tea (Camellia ptilophylla) induces mitochondria-dependent apoptosis in HCT116 cells via ROS generation and PI3K/Akt signaling pathway

Xiong Gao; Xiaofei Li; Chi-Tang Ho; Xiaorong Lin; Yuanyuan Zhang; Bin Li; Zhongzheng Chen

doi:10.1016/j.foodres.2019.108854

Cocoa tea (Camellia ptilophylla) induces mitochondria-dependent apoptosis in HCT116 cells via ROS generation and PI3K/Akt signaling pathway

Food Res Int. 2020 Mar:129:108854. doi: 10.1016/j.foodres.2019.108854. Epub 2019 Dec 2.

Authors

Xiong Gao¹, Xiaofei Li², Chi-Tang Ho³, Xiaorong Lin², Yuanyuan Zhang², Bin Li⁴, Zhongzheng Chen⁵

Affiliations

¹ State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China.
² College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China.
³ Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA.
⁴ College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China. Electronic address: bli@scau.edu.cn.
⁵ College of Food Science, South China Agricultural University, Tianhe District, 483 Wushan Street, Guangzhou 510642, China. Electronic address: zhongzhengch@scau.edu.cn.

PMID: 32036895
DOI: 10.1016/j.foodres.2019.108854

Abstract

Cocoa tea (Camellia ptilophylla), a natural gallocatechin gallate (GCG)-rich and low caffeine-containing tea species, has been recently reported to possess various bioactivities. However, the anti-colon cancer effects of Cocoa tea and its underlying mechanisms remain virtually unknown. This study aimed to assess the anti-proliferative and pro-apoptotic effects of water extract of Cocoa tea (CWE) on human colon cancer HCT116 cells compared with Yunnan Daye tea (YWE). Primarily, CWE showed stronger anti-proliferation and apoptosis induction than YWE. Moreover, reduction of mitochondrial membrane potential (MMP), up-regulation of Bax/Bcl-2 ratio, release of cytochrome c, activation of caspase-9 and -3, and cleavage of poly (ADP-ribose) polymerase (PARP) were observed, suggesting that mitochondrial apoptotic pathway was activated by CWE. Furthermore, CWE-induced apoptosis in HCT116 cells was dependent on the generation of intracellular reactive oxygen species (ROS) and down-regulation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Pretreatment with ROS scavenger N-acetyl cysteine (NAC) attenuated the impact of CWE on mitochondria-related apoptosis proteins, and partially recovered the inhibition of Akt phosphorylation. These results indicated that ROS generation mediated mitochondrial dysfunction and inactivation of PI3K/Akt pathway in CWE-induced HCT116 cell apoptosis. Additionally, CWE significantly inhibited tumor growth in HCT116 tumor-bearing mice, suggesting that Cocoa tea could act as a potential functional beverage to prevent or treat colorectal cancer.

Keywords: Apoptosis; Cocoa tea; Colon cancer; GCG-rich; HCT116 cells; Low-caffeine; PI3K/Akt; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Beverages / analysis
Camellia / classification*
Cell Survival / drug effects
Gene Expression Regulation / drug effects
HCT116 Cells
Humans
Male
Mice
Mice, Nude
Mitochondria / metabolism*
Neoplasms, Experimental / drug therapy
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
Reactive Oxygen Species / metabolism*

Substances

Reactive Oxygen Species
Proto-Oncogene Proteins c-akt