Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species.

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 Ca(2+) concentration ([Ca(2+)](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 p47(phox) and p67(phox) subunits and shown to be necessary for ROS generation by panaxydol treatment. Panaxydol triggered a rapid and sustained increase of [Ca(2+)](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 p47(phox) and p67(phox) subunits and ROS generation. In summary, these data indicate that panaxydol induces apoptosis preferentially in cancer cells, and the signaling mechanisms involve a [Ca(2+)](i) increase, JNK and p38 MAPK activation, and ROS generation through NADPH oxidase and mitochondria.

• Authors: Joo Young Kim, Su-Jin Yu, Hyun Ju Oh, Ji Young Lee, Yongjin Kim, Jeongwon Sohn
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 16 Issue 4 Pg. 347-58 (Apr 2011) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 21190085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diynes
• Fatty Alcohols
• Reactive Oxygen Species
• panaxydol
• NADPH Oxidases
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspases
• Calcium

Topics

• Apoptosis (drug effects)
• Calcium (metabolism)
• Caspases (metabolism)
• Cell Line, Transformed
• Diynes (pharmacology)
• Enzyme Activation (drug effects)
• Fatty Alcohols (pharmacology)
• Humans
• Intracellular Space (drug effects, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mitochondria (drug effects, enzymology)
• NADPH Oxidases (metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)