[10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells.

Abstract

The present study was designed to investigate the molecular mechanisms of [10]-gingerol activity against HCT116 human colon cancer cells. [10]-Gingerol inhibited the proliferation of HCT116 cells by 50% at a concentration of 30 μM, and this inhibition was dose-dependent accompanied by the morphological changes indicative of apoptosis. Furthermore, flow cytometric analysis showed that [10]-gingerol increased DNA in the sub-G1 phase of the cell cycle, and the extent of apoptosis was confirmed by Annexin V and PI double staining. Analysis of the mechanism of these events indicated that [10]-gingerol-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner, which are hallmarks of apoptosis. Moreover, [10]-gingerol-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase (MAPKs) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). This is the first report to demonstrate the cytotoxic effect of [10]-gingerol on human colon cancer cells, as well as the first to describe its possible chemotherapeutic potentials.

• Authors: Min Ju Ryu, Ha Sook Chung
• Journal: In vitro cellular & developmental biology. Animal (In Vitro Cell Dev Biol Anim) Vol. 51 Issue 1 Pg. 92-101 (Jan 2015) ISSN: 1543-706X [Electronic] Germany
• PMID: 25148824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechols
• Fatty Alcohols
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• gingerol
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspase 3

Topics

• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Catechols (chemistry, pharmacology)
• Cell Cycle (drug effects)
• Colonic Neoplasms (enzymology, pathology)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fatty Alcohols (chemistry, pharmacology)
• HCT116 Cells
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mitochondria (drug effects, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• bcl-2-Associated X Protein (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)