Maslinic acid induces mitochondrial apoptosis and suppresses HIF-1α expression in A549 lung cancer cells under normoxic and hypoxic conditions.

Abstract

The apoptotic effects of maslinic acid (MA) at 4, 8, 16, 32 and 64 μmol/L on human lung cancer A549 cells under normoxic and hypoxic conditions were examined. MA at 4-64 and 16-64 μmol/L lowered Bcl-2 expression under normoxic and hypoxic conditions, respectively (p < 0.05). This agent at 4-64 μmol/L decreased Na+-K+-ATPase activity and increased caspase-3 expression under normoxic conditions, but at 8-64 μmol/L it caused these changes under hypoxic conditions (p < 0.05). MA up-regulated caspase-8, cytochrome c and apoptosis-inducing factor expression under normoxic and hypoxic conditions at 8-64 μmol/L and 32-64 μmol/L, respectively (p < 0.05). MA down-regulated hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), survivin and inducible nitric oxide synthase (iNOS) expression under normoxic and hypoxic conditions at 8-64 and 16-64 μmol/L, respectively (p < 0.05). After cells were pre-treated with YC-1, an inhibitor of HIF-1α, MA failed to affect the protein expression of HIF-1α, VEGF, survivin and iNOS (p > 0.05). MA at 8-64 and 32-64 μmol/L reduced reactive oxygen species and nitric oxide levels under both conditions (p < 0.05). These findings suggest that maslinic acid, a pentacyclic triterpenic acid, exerted its cytotoxic activities toward A549 cells by mediating mitochondrial apoptosis and the HIF-1α pathway.

• Authors: Te-Chun Hsia, Wen-Hu Liu, Wen-Wei Qiu, Jian Luo, Mei-Chin Yin
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 19 Issue 12 Pg. 19892-906 (Nov 28 2014) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25460312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Inducing Factor
• BIRC5 protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Inhibitor of Apoptosis Proteins
• Reactive Oxygen Species
• Survivin
• Triterpenes
• bcl-2-Associated X Protein
• Nitric Oxide
• Cytochromes c
• maslinic acid
• NOS2 protein, human
• Nitric Oxide Synthase Type II
• Caspase 3
• Caspase 8
• Sodium-Potassium-Exchanging ATPase

Topics

• Apoptosis (drug effects)
• Apoptosis Inducing Factor (metabolism)
• Bronchi (pathology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• Cytosol (drug effects, metabolism)
• Epithelial Cells (drug effects, enzymology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Inhibitor of Apoptosis Proteins (metabolism)
• Lung Neoplasms (metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Survivin
• Triterpenes (pharmacology)
• bcl-2-Associated X Protein (metabolism)