Oleifolioside B-mediated autophagy promotes apoptosis in A549 human non-small cell lung cancer cells.

Abstract

The biochemical mechanisms of cell death by oleifolioside B (OB), a cycloartane-type triterpene glycoside isolated from Dendropanax morbifera Leveille, were investigated in A549 human lung carcinoma cells. Our data indicated that exposure to OB led to caspase activation and typical features of apoptosis; however, apoptotic cell death was not prevented by z-VAD-fmk, a pan-caspase inhibitor, demonstrating that OB-induced apoptosis was independent of caspase activation. Subsequently, we found that OB increased autophagy, as indicated by an increase in monodansylcadaverine fluorescent dye-labeled autophagosome formation and in the levels of the autophagic form of microtubule-associated protein 1 light chain 3 and Atg3, an autophagy-specific gene, which is associated with inhibiting phospho-nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, pretreatment with bafilomycin A1, an autophagy inhibitor, attenuated OB-induced apoptosis and dephosphorylation of Nrf2. The data suggest that OB-induced autophagy functions as a death mechanism in A549 cells and OB has potential as a novel anticancer agent capable of targeting apoptotic and autophagic cell death and the Nrf2 signaling pathway.

• Authors: Cheng-Yun Jin, Hai Yang Yu, Cheol Park, Min Ho Han, Su Hyun Hong, Kyoung-Sook Kim, Young-Choon Lee, Young-Chae Chang, Jaehun Cheong, Sung-Kwon Moon, Gi-Young Kim, Hyung-In Moon, Wun-Jae Kim, Jai-Heon Lee, Yung Hyun Choi
• Journal: International journal of oncology (Int J Oncol) Vol. 43 Issue 6 Pg. 1943-50 (Dec 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24141596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Antineoplastic Agents
• Autophagy-Related Proteins
• BIRC5 protein, human
• CASP8 and FADD-Like Apoptosis Regulating Protein
• Caspase Inhibitors
• Enzyme Inhibitors
• Inhibitor of Apoptosis Proteins
• MAP1LC3A protein, human
• Macrolides
• Microtubule-Associated Proteins
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• Saponins
• Survivin
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• oleifolioside B
• bafilomycin A1
• Ubiquitin-Conjugating Enzymes
• Caspase 3
• Caspase 8
• Caspase 9
• ATG3 protein, human

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Autophagy-Related Proteins
• CASP8 and FADD-Like Apoptosis Regulating Protein (biosynthesis)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Caspase Inhibitors (pharmacology)
• Cell Line, Tumor
• Enzyme Inhibitors (pharmacology)
• Humans
• Inhibitor of Apoptosis Proteins (biosynthesis)
• Lung Neoplasms (drug therapy)
• Macrolides (pharmacology)
• Microtubule-Associated Proteins (biosynthesis, metabolism)
• NF-E2-Related Factor 2 (biosynthesis, metabolism)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Saponins (pharmacology)
• Survivin
• Ubiquitin-Conjugating Enzymes (biosynthesis, metabolism)