Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species
- 30 December 2010
- journal article
- Published by Springer Nature in Apoptosis
- Vol. 16 (4), 347-358
- https://doi.org/10.1007/s10495-010-0567-8
Abstract
Panaxydol, a polyacetylenic compound derived from Panax ginseng roots, has been shown to inhibit the growth of cancer cells. In this study, we demonstrated that panaxydol induced apoptosis preferentially in transformed cells with a minimal effect on non-transformed cells. Furthermore, panaxydol was shown to induce apoptosis through an increase in intracellular Ca2+ concentration ([Ca2+]i), activation of JNK and p38 MAPK, and generation of reactive oxygen species (ROS) initially by NADPH oxidase and then by mitochondria. Panaxydol-induced apoptosis was caspase-dependent and occurred through a mitochondrial pathway. ROS generation by NADPH oxidase was critical for panaxydol-induced apoptosis. Mitochondrial ROS production was also required, however, it appeared to be secondary to the ROS generation by NADPH oxidase. Activation of NADPH oxidase was demonstrated by the membrane translocation of regulatory p47phox and p67phox subunits and shown to be necessary for ROS generation by panaxydol treatment. Panaxydol triggered a rapid and sustained increase of [Ca2+]i, which resulted in activation of JNK and p38 MAPK. JNK and p38 MAPK play a key role in activation of NADPH oxidase, since inhibition of their expression or activity abrogated membrane translocation of p47phox and p67phox subunits and ROS generation. In summary, these data indicate that panaxydol induces apoptosis preferentially in cancer cells, and the signaling mechanisms involve a [Ca2+]i increase, JNK and p38 MAPK activation, and ROS generation through NADPH oxidase and mitochondria.Keywords
This publication has 33 references indexed in Scilit:
- NADPH oxidase is the primary source of superoxide induced by NMDA receptor activationNature Neuroscience, 2009
- PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell DeathMolecular Cell, 2009
- Identification of potential lung cancer biomarkers using an in vitro carcinogenesis modelExperimental & Molecular Medicine, 2008
- Glycogen Synthase Kinase 3β Phosphorylates p21WAF1/CIP1 for Proteasomal Degradation after UV IrradiationMolecular and Cellular Biology, 2007
- Mitochondria, oxidative stress and cell deathApoptosis, 2007
- Mechanisms of Cell Death in Oxidative StressAntioxidants and Redox Signaling, 2007
- Nox2, Ca 2+ , and Protein Kinase C Play a Role in Angiotensin II-Induced Free Radical Production in Nucleus Tractus SolitariusHypertension, 2006
- BAX and BAK Regulation of Endoplasmic Reticulum Ca 2+ : A Control Point for ApoptosisScience, 2003
- Relationship between p38 mitogen-activated protein kinase and small GTPase Rac for the activation of NADPH oxidase in bovine neutrophilsBiochemical and Biophysical Research Communications, 2002
- Oxidative stress as a mediator of apoptosisImmunology Today, 1994