Article Publish Status: FREE
Abstract Title:

Piperlongumine and immune cytokine TRAIL synergize to promote tumor death.

Abstract Source:

Sci Rep. 2015 ;5:9987. Epub 2015 May 18. PMID: 25984950

Abstract Author(s):

Jiahe Li, Charles C Sharkey, Michael R King

Article Affiliation:

Jiahe Li


Malignant transformation results in increased levels of reactive oxygen species (ROS). Adaption to this toxic stress allows cancer cells to proliferate. Recently, piperlongumine (PL), a natural alkaloid, was identified to exhibit novel anticancer effects by targeting ROS signaling. PL induces apoptosis specifically in cancer cells by downregulating several anti-apoptotic proteins. Notably, the same anti-apoptotic proteins were previously found to reduce tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in cancer cells. Therefore, we reasoned that PL would synergize with TRAIL to stimulate potent apoptosis in cancer cells. We demonstrate for the first time that PL and TRAIL exhibit a synergistic anti-cancer effect in cancer cell lines of various origins. PL resulted in the upregulation of TRAIL receptor DR5, which potentiated TRAIL-induced apoptosis in cancer cells. Furthermore, such upregulation was found to be dependent on ROS and the activation of JNK and p38 kinases. Treatment with combined PL and TRAIL demonstrated significant anti-proliferative effects in a triple-negative breast cancer MDA-MB-231 xenograft model. This work provides a novel therapeutic approach for inducing cancer cell death. Combination of PL and TRAIL may suggest a novel paradigm for treatment of primary and metastatic tumors.

Print Options

Sayer Ji
Founder of

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022, Journal Articles copyright of original owners, MeSH copyright NLM.