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- Title
Lithium enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells.
- Authors
Lan, Yan; Liu, Xiufeng; Zhang, Rong; Wang, Kai; Wang, Yao; Hua, Zi-Chun
- Abstract
Non-small cell lung cancer (NSCLC) A549 cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Therefore, combination therapy using sensitizing agents to overcome TRAIL resistance may provide new strategies for treatment of NSCLC. Here, we investigated whether lithium chloride (LiCl), a drug for mental illness, could sensitize A549 cells to TRAIL-induced apoptosis. We observed that LiCl significantly enhanced A549 cells apoptosis through up-regulation of death receptors DR4 and DR5 and activation of caspase cascades. In addition, G2/M arrest induced by LiCl also contributed to TRAIL-induced apoptosis. Concomitantly, LiCl strongly inhibited the activity of c-Jun N-terminal kinases (JNKs), and the inhibition of JNKs by SP600125 also induced G2/M arrest and augmented cell death caused by TRAIL or TRAIL plus LiCl. However, glycogen synthase kinase-3β (GSK3β) inhibition was not involved in TRAIL sensitization induced by LiCl. Collectively, these findings indicated that LiCl sensitized A549 cells to TRAIL-induced apoptosis through caspases-dependent apoptotic pathway via death receptors signaling and G2/M arrest induced by inhibition of JNK activation, but independent of GSK3β.
- Subjects
LITHIUM; SMALL cell lung cancer; APOPTOSIS; TUMOR necrosis factors; APOPTOSIS inducing factor; LITHIUM chloride
- Publication
BioMetals, 2013, Vol 26, Issue 2, p241
- ISSN
0966-0844
- Publication type
Article
- DOI
10.1007/s10534-012-9607-x