| Title |
Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells
|
|---|---|
| Published in |
Drug Design, Development and Therapy, February 2015
|
| DOI | 10.2147/dddt.s73493 |
| Pubmed ID | |
| Authors |
Yan-Yang Wang, Yin-Xue Yang, Ren Zhao, Shu-Ting Pan, Hong Zhe, Zhi-Xu He, Wei Duan, Xueji Zhang, Tianxin Yang, Jia-Xuan Qiu, Shu-Feng Zhou |
| Abstract |
Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me) on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC) cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl), B-cell lymphoma 2 (Bcl-2), cleaved caspase-9, and cleaved poly ADP ribose polymerase (PARP) levels but increased the expression level of Bcl-2-associated X (Bax). Furthermore, CDDO-Me induced autophagy in both Ec109 and KYSE70 cells via suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. There were interactions between the autophagic and apoptotic pathways in Ec109 and KYSE70 cells subject to CDDO-Me treatment. CDDO-Me also scavenged reactive oxygen species through activation of the nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) pathway in Ec109 and KYSE70 cells. CDDO-Me inhibited cell invasion, epithelial-mesenchymal transition, and stemness in Ec109 and KYSE70 cells. CDDO-Me significantly downregulated E-cadherin but upregulated Snail, Slug, and zinc finger E-box-binding homeobox 1 (TCF-8/ZEB1) in Ec109 and KYSE70 cells. CDDO-Me significantly decreased the expression of octamer-4, sex determining region Y-box 2 (Sox-2), Nanog, and B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), all markers of cancer cell stemness, in Ec109 and KYSE70 cells. Taken together, these results indicate that CDDO-Me is a promising anticancer agent against ESCC. Further studies are warranted to explore the molecular targets, efficacy and safety of CDDO-Me in the treatment of ESCC. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 2% |
| Unknown | 41 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 7 | 17% |
| Researcher | 7 | 17% |
| Student > Ph. D. Student | 2 | 5% |
| Professor | 2 | 5% |
| Student > Master | 2 | 5% |
| Other | 2 | 5% |
| Unknown | 20 | 48% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 17% |
| Biochemistry, Genetics and Molecular Biology | 5 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
| Agricultural and Biological Sciences | 3 | 7% |
| Nursing and Health Professions | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 22 | 52% |
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 04 March 2015.
All research outputs
#19,916,939
of 25,371,288 outputs
Outputs from Drug Design, Development and Therapy
#1,308
of 2,268 outputs
Outputs of similar age
#254,022
of 361,157 outputs
Outputs of similar age from Drug Design, Development and Therapy
#36
of 62 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,268 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 42nd percentile – i.e., 42% 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 361,157 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 62 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.