Maslinic Acid Induces Mitochondrial Apoptosis and Suppresses HIF-1α Expression in A549 Lung Cancer Cells under Normoxic and Hypoxic Conditions

Molecules

Te-Chun Hsia¹  Wen-Hu Liu²  Wen-Wei Qiu³  Jian Luo⁵  Mei-Chin Yin⁴ 

[1] Department of Respiratory Therapy, China Medical University, Taichung 40402, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan;;Institute of Medicinal Chemistry and Department of Chemistry, East China Normal University, Shanghai 200241, China;Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan;Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China

关键词: maslinic acid;    lung cancer;    HIF-1α;    mitochondrial apoptosis;   

DOI  :  10.3390/molecules191219892

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.