Houttuynia cordata Thunb Fraction Induces Human Leukemic Molt-4 Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway

Adchara Prommaban,Ratana Banjerdpongchai,Prachya Kongtawelert,Kanchanok Kodchakorn

doi:10.7314/apjcp.2012.13.5.1977

Adchara Prommaban, Ratana Banjerdpongchai + Show 2 more

Open Access

https://doi.org/10.7314/apjcp.2012.13.5.1977

Copy DOI

Abstract

Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with IC50 of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway.

Highlights

Apoptosis is a programmed cell death found in both the physiological and pathological processes such as sloughing off of the gastrointestinal epithelium, neurological degenerative diseases, autoimmune diseases and infection
Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer
The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death

Summary

Introduction

Apoptosis is a programmed cell death found in both the physiological and pathological processes such as sloughing off of the gastrointestinal epithelium, neurological degenerative diseases, autoimmune diseases and infection. Bax and Bak, proapoptotic protein in the Bcl-2 family, form homodimers at the mitochondrial membrane and cause the release of cytochromec, Smac/Diablo, and apoptosis inducing factor (AIF). Endoplasmic reticulum (ER) is an organelle responsible to the posttranslational modification of proteins It controls protein folding by chaperones and the process of protein glycation. Three types of ER membrane receptors, ATF6, IRE1 and PERK, sense the stress in the ER, and eventually activate transcription factors for induction of ER chaperones, such as GRP78, for inhibition of synthesis of new proteins. These processes are called unfolded protein response (UPR) (Imaizumi et al, 2001). Apaf-1 and the mitochondrial pathway of apoptosis play significant roles in ER stress-induced apoptosis (Shiraishi et al, 2006)

Objectives

Methods

Results