Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a primary anticancer agent and a member of the tumor necrosis factor family that selectively induces apoptosis in various tumor cells, but not in normal cells. Gingerol is a major ginger component with anti-inflammatory and anti‑tumorigenic activities. Autophagy flux is the complete process of autophagy, in which the autophagosomes are lysed by lysosomes. The role of autophagy in cell death or cell survival is controversial. A549 adenocarcinoma cells are TRAIL-resistant. In the present study, we showed that treatment with TRAIL slightly induced cell death, but gingerol treatment enhanced the TRAIL-induced cell death in human lung cancer cells. The combination of gingerol and TRAIL increased accumulation of microtubule-associated protein light chain 3-II and p62, confirming the inhibited autophagy flux. Collectively, our results suggest that gingerol sensitizes human lung cancer cells to TRAIL-induced apoptosis by inhibiting the autophagy flux.

• Authors: Uddin Md Nazim, Jae-Kyo Jeong, Jae-Won Seol, Jin Hur, Seong-Kug Eo, John-Hwa Lee, Sang-Youel Park
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 5 Pg. 2331-6 (May 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25813697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Autophagy-Related Protein 8 Family
• Catechols
• Fatty Alcohols
• GABARAPL2 protein, human
• Microfilament Proteins
• SQSTM1 protein, human
• Sequestosome-1 Protein
• TNF-Related Apoptosis-Inducing Ligand
• gingerol

Topics

• Adaptor Proteins, Signal Transducing (drug effects, metabolism)
• Adenocarcinoma (metabolism)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Autophagy-Related Protein 8 Family
• Catechols (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Fatty Alcohols (pharmacology)
• Humans
• Lung Neoplasms (metabolism)
• Microfilament Proteins (drug effects, metabolism)
• Sequestosome-1 Protein
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)