Evidence map›Paper›PMID 27465411›Full record

ArticleBMC cancer2016

PAC down-regulates estrogen receptor alpha and suppresses epithelial-to-mesenchymal transition in breast cancer cells.

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

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 24 citations in OpenAlex.

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  11. Curcumin: a potent agent to reverse epithelial-to-mesenchymal transition.Cellular oncology (Dordrecht, Netherlands) · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Huda A Al-HowailDepartment of Molecular Oncology, King Faisal Specialist Hospital and Research Center, MBC # 03, PO BOX 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
Hana A HakamiDepartment of Molecular Oncology, King Faisal Specialist Hospital and Research Center, MBC # 03, PO BOX 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
Basem Al-OtaibiDepartment of Cyclotron and Radiopharmaceuticals, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Kingdom of Saudi Arabia.
Amer Al-MazrouStem Cell Therapy Program, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Kingdom of Saudi Arabia.
Maha H DaghestaniDepartment of Zoology, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Ibrahim Al-JammazDepartment of Cyclotron and Radiopharmaceuticals, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Kingdom of Saudi Arabia.
Huda H Al-KhalafDepartment of Molecular Oncology, King Faisal Specialist Hospital and Research Center, MBC # 03, PO BOX 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
Abdelilah AboussekhraDepartment of Molecular Oncology, King Faisal Specialist Hospital and Research Center, MBC # 03, PO BOX 3354, Riyadh, 11211, Kingdom of Saudi Arabia. aboussekhra@kfshrc.edu.sa.
King Faisal Specialist Hospital & Research Centre · SAKing Saud University · SA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTriple-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.

methodsHPLC 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.

resultsPAC 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.

conclusionThese results indicate that PAC could be considered as important candidate for future therapeutic options against the devastating TNBC subtype.

Indexed as

AnimalsAntineoplastic AgentsBenzylidene CompoundsCell Line, TumorCell ProliferationCell SurvivalChemokine CCL2CurcuminDrug StabilityEpithelial-Mesenchymal TransitionEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticHumansInterleukin-6Mice5-bis(4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidoneAntineoplastic AgentsBenzylidene CompoundsCCL2 protein, humanChemokine CCL2CurcuminESR1 protein, humanEstrogen Receptor alphaIL6 protein, humanInterleukin-6PiperidonesBreast cancerEMTERαPAC

Identifiers

PMID27465411
PMCPMC4964287
OpenAlexW2478825408

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.