Flavonoids from Orostachys japonicus A. Berger induces caspase-dependent apoptosis at least partly through activation of p38 MAPK pathway in U937 human leukemic cells.

Won Sup Lee,Arulkumar Nagappan,Gonsup Kim,Chung Ho Ryu,Jin-Myung Jung,Soon Chan Hong,Hye Jung Kim,Sang Mi Yi,Dong Hoon Kim,Yung Hyun Choi,Sung Chul Shin,Ji Hyun Jung,Jeong Won Yun

doi:10.7314/apjcp.2015.16.2.465

Abstract

Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. U937 human leukemic cancer cells were used. FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of 200 μg/mL and 400 μg/mL. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ΔΨm) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (ΔΨm) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.

Highlights

Apoptosis is an active-energy requiring process with a distinctive phenotype characterized by cytoplasmic shrinkage, blebbing of the plasma membrane, chromatin condensation, DNA degradation, and nuclear fragmentation (Kerr et al, 1972; Walker and Sikorska, 1997)
We investigated whether flavonoids extracted from Orostachys japonicus A
FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ΔΨm) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and X-linked IAP (XIAP) proteins

Summary

Introduction

Apoptosis is an active-energy requiring process (a type I programmed cell death) with a distinctive phenotype characterized by cytoplasmic shrinkage, blebbing of the plasma membrane, chromatin condensation, DNA degradation, and nuclear fragmentation (Kerr et al, 1972; Walker and Sikorska, 1997). One of the pragmatic ways is chemoprevention because the dietary agents and some phytochemicals are reported to induce apoptosis or enhance anti-cancer effects without significant toxicities in the normal cells (Palasap et al, 2014). Berger (FEOJ) and the molecular mechanisms of the effects are poorly understood in human cancer cells. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ΔΨm) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (ΔΨm) through suppressing Bcl-2 and X-IAP. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells

Methods

Results

Conclusion