Xiao-ke Shi, Xiao-bo Bian, Tao Huang, Bo Wen, Ling Zhao, Huai-xue Mu, Sarwat Fatima, Bao-min Fan, Zhao-xiang Bian, Lin-fang Huang, Cheng-yuan Lin
Abstract
Recent studies indicate that mitochondrial pathways of apoptosis are potential chemotherapeutic target for the treatment of esophageal cancer. Azoxystrobin (AZOX), a methoxyacrylate derived from the naturally occurring strobilurins, is a known fungicide acting as a ubiquinol oxidation (Qo) inhibitor of mitochondrial respiratory complex III. In this study, the effects of AZOX on human esophageal squamous cell carcinoma KYSE-150 cells were examined and the underlying mechanisms were investigated. AZOX exhibited inhibitory effects on the proliferation of KYSE-150 cells with inhibitory concentration 50% (IC50) of 2.42 μg/ml by 48 h treatment. Flow cytometry assessment revealed that the inhibitory effect of AZOX on KYSE-150 cell proliferation occurred with cell cycle arrest at S phase and increased cell apoptosis in time-dependent and dose-dependent manners. Cleaved poly ADP ribose polymerase (PARP), caspase-3 and caspase-9 were increased significantly by AZOX. It is worth noted that the Bcl-2/Bax ratios were decreased because of the down-regulated Bcl-2 and up-regulated Bax expression level. Meanwhile, the cytochrome c release was increased by AZOX in KYSE-150 cells. AZOX-induced cytochrome c expression and caspase-3 activation was significantly blocked by Bax Channel Blocker. Intragastric administration of AZOX effectively decreased the tumor size generated by subcutaneous inoculation of KYSE-150 cells in nude mice. Consistently, decreased Bcl-2 expression, increased cytochrome c and PARP level, and activated caspase-3 and caspase-9 were observed in the tumor samples. These results indicate that AZOX can effectively induce esophageal cancer cell apoptosis through the mitochondrial pathways of apoptosis, suggesting AZOX or its derivatives may be developed as potential chemotherapeutic agents for the treatment of esophageal cancer.
Pharmacology, Toxicology and Pharmaceutical Science
4
27%
Biochemistry, Genetics and Molecular Biology
3
20%
Medicine and Dentistry
1
7%
Unknown
7
47%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2017.
All research outputs
#18,547,867
of 22,971,207 outputs
Outputs from Frontiers in Pharmacology
#8,318
of 16,251 outputs
Outputs of similar age
#238,993
of 313,744 outputs
Outputs of similar age from Frontiers in Pharmacology
#136
of 252 outputs
Altmetric has tracked 22,971,207 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,251 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 313,744 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 252 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
