Reactive oxygen species contribute to TRAIL receptors upregulation; the mechanism for PH II-7 augmenting TRAIL induced apoptosis in leukemia cells

Hongwei Peng; Xiangfei Yuan; Shiwen Luo; Fei Li; Xiaohua Wei; Zhou Ye; Dongsheng Xiong

doi:10.1016/j.ejphar.2014.10.028

Reactive oxygen species contribute to TRAIL receptors upregulation; the mechanism for PH II-7 augmenting TRAIL induced apoptosis in leukemia cells

Eur J Pharmacol. 2015 Jan 5:746:344-52. doi: 10.1016/j.ejphar.2014.10.028. Epub 2014 Nov 15.

Authors

Hongwei Peng¹, Xiangfei Yuan², Shiwen Luo³, Fei Li⁴, Xiaohua Wei⁵, Zhou Ye⁶, Dongsheng Xiong⁷

Affiliations

¹ Department of Pharmacy, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China; State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, PR China.
² State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, PR China.
³ Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Institute of Life Sciences, Nanchang University, Nanchang, Jiangxi 330006, PR China.
⁴ Department of Hematology, First affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
⁵ Department of Pharmacy, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China. Electronic address: wxh-hello@163.com.
⁶ Central Hospital of Karamay, Karamay, Xinjiang 834000, PR China. Electronic address: yezhou126@126.com.
⁷ State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, PR China. Electronic address: dsxiong@ihcams.ac.cn.

PMID: 25446561
DOI: 10.1016/j.ejphar.2014.10.028

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells and is verified to be effective in various cancers. However, a variety of cancer cells are found to be resistant to TRAIL and the mechanisms are largely unknown. Moreover, multidrug resistance to traditional chemotherapeutic agents still remains a tough problem in clinical practice. Fortunately, our previous work proved the ability of PH II-7 in overcoming MDR phenotype through reactive oxygen species production in K562 and its MDR counterpart K562/A02 cells. Additionally, we further explored its potential in augmenting TRAIL induced apoptosis in cancer cells with various tissue origins. Our results showed PH II-7 up-regulated DR4/DR5 expression and augment TRAIL cytotoxicity through reactive oxygen species production, which provide a solid foundation for TRAIL in combination with PH II-7 in future clinical application.

Keywords: Apoptosis; Multidrug resistance; PH II-7; Reactive oxygen species; Tumor necrosis factor related apoptosis inducing ligand (TRAIL).

Publication types

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

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Line, Tumor
Cell Survival / drug effects
Drug Resistance, Neoplasm
Gene Expression Regulation, Leukemic / drug effects
Humans
Indoles / pharmacology*
Leukemia / drug therapy*
Leukemia / metabolism
Leukemia / pathology
Oxidative Stress / drug effects
Peptide Fragments / agonists
Peptide Fragments / antagonists & inhibitors
Peptide Fragments / genetics
Peptide Fragments / metabolism
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering
Reactive Oxygen Species / metabolism*
Receptors, TNF-Related Apoptosis-Inducing Ligand / agonists*
Receptors, TNF-Related Apoptosis-Inducing Ligand / antagonists & inhibitors
Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
Solubility
Up-Regulation / drug effects*

Substances

Antineoplastic Agents
Indoles
PHII-7 compound
Peptide Fragments
RNA, Messenger
RNA, Small Interfering
Reactive Oxygen Species
Receptors, TNF-Related Apoptosis-Inducing Ligand
TNFRSF10A protein, human
TNFRSF10B protein, human