| Title |
PAC down-regulates estrogen receptor alpha and suppresses epithelial-to-mesenchymal transition in breast cancer cells
|
|---|---|
| Published in |
BMC Cancer, July 2016
|
| DOI | 10.1186/s12885-016-2583-8 |
| Pubmed ID | |
| Authors |
Huda A. Al-Howail, Hana A. Hakami, Basem Al-Otaibi, Amer Al-Mazrou, Maha H. Daghestani, Ibrahim Al-Jammaz, Huda H. Al-Khalaf, Abdelilah Aboussekhra |
| Abstract |
Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Therefore, novel molecules and therapeutic options are urgently needed for this category of patients. Recently, we have identified PAC as a curcumin analogue with potent anti-cancer features. HPLC was used to evaluate the stability of PAC and curcumin in PBS and also in circulating blood. Cytotoxicity/apoptosis was assessed in different breast cancer cell lines using propidium iodide/annexinV associated with flow cytometry. Furthermore, immunoblotting analysis determined the effects of PAC on different oncogenic proteins and pathways. Additionally, the real time xCELLigence RTCA technology was applied to investigate the effect of PAC on the cellular proliferation, migration and invasion capacities. PAC is more stable than curcumin in PBS and in circulating blood. Furthermore, we have shown differential sensitivity of estrogen receptor-alfa positive (ERα(+)) and estrogen receptor alfa negative (ERα(-)) breast cancer cells to PAC, which down-regulated ERα in both cell types. This led to complete disappearance of ERα in ERα(-) cells, which express very low level of this receptor. Interestingly, specific down-regulation of ERα in receptor positive cells increased the apoptotic response of these cells to PAC, confirming that ERα inhibits PAC-dependent induction of apoptosis, which could be mediated through ERα down-regulation. Additionally, PAC inhibited the proliferation and suppressed the epithelial-to-mesenchymal transition process in breast cancer cells, with higher efficiency on the TNBC subtype. This effect was also observed in vivo on tumor xenografts. Additionally, PAC suppressed the expression/secretion of 2 important cytokines IL-6 and MCP-1, and consequently inhibited the paracrine procarcinogenic effects of breast cancer cells on breast stromal fibroblasts. These results indicate that PAC could be considered as important candidate for future therapeutic options against the devastating TNBC subtype. |
X Demographics
The data shown below were collected from the profiles of 71 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Saudi Arabia | 37 | 52% |
| United States | 1 | 1% |
| Unknown | 33 | 46% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 60 | 85% |
| Practitioners (doctors, other healthcare professionals) | 5 | 7% |
| Scientists | 4 | 6% |
| Science communicators (journalists, bloggers, editors) | 1 | 1% |
| Unknown | 1 | 1% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Slovenia | 1 | 3% |
| Unknown | 28 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 20% |
| Researcher | 5 | 17% |
| Student > Master | 4 | 13% |
| Student > Ph. D. Student | 3 | 10% |
| Librarian | 1 | 3% |
| Other | 2 | 7% |
| Unknown | 9 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 17% |
| Medicine and Dentistry | 3 | 10% |
| Immunology and Microbiology | 3 | 10% |
| Agricultural and Biological Sciences | 2 | 7% |
| Nursing and Health Professions | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 13 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 52. 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 12 May 2018.
All research outputs
#822,385
of 25,748,735 outputs
Outputs from BMC Cancer
#101
of 9,069 outputs
Outputs of similar age
#15,943
of 381,387 outputs
Outputs of similar age from BMC Cancer
#3
of 258 outputs
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