Abstract |
Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer- binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.
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Authors | Eun Jin Lim, Yu Jeong Yoon, Jeonghoon Heo, Tae Hwa Lee, Young-Ho Kim |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 19
Issue 10
(Oct 16 2018)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 30332761
(Publication Type: Journal Article)
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Chemical References |
- Receptors, Death Domain
- TNF-Related Apoptosis-Inducing Ligand
- Transcription Factor CHOP
- Ciprofloxacin
- Caspases
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Topics |
- Apoptosis
(drug effects)
- Caspases
(metabolism)
- Cell Line, Tumor
- Ciprofloxacin
(pharmacology)
- Drug Synergism
- Enzyme Activation
(drug effects)
- Gene Knockdown Techniques
- Humans
- Lung Neoplasms
(pathology)
- Protein Stability
(drug effects)
- Receptors, Death Domain
(metabolism)
- TNF-Related Apoptosis-Inducing Ligand
(pharmacology)
- Transcription Factor CHOP
(metabolism)
- Up-Regulation
(drug effects)
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