ArticleThe Journal of biological chemistry2015
Cross-talk between endoplasmic reticulum (ER) stress and the MEK/ERK pathway potentiates apoptosis in human triple negative breast carcinoma cells: role of a dihydropyrimidone, nifetepimine.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting programmed cell death pathways: emerging therapeutic strategies for diabetic kidney disease.Frontiers in endocrinology · 2025Review
- Small Molecule Therapeutics in the Pipeline Targeting for Triple-Negative Breast Cancer: Origin, Challenges, Opportunities, and Mechanisms of Action.International journal of molecular sciences · 2024Review
- Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.Cell death discovery · 2024Article
- Review
- Synergistic antitumor effect of a penicillin derivative combined with thapsigargin in melanoma cells.Journal of cancer research and clinical oncology · 2022Article
- mTOR pathway mediates endoplasmic reticulum stress-induced CD4Apoptosis : an international journal on programmed cell death · 2022Article
- A Signature of Three Apoptosis-Related Genes Predicts Overall Survival in Breast Cancer.Frontiers in surgery · 2022Article
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- Article
- Mi-RNA-888-5p Is Involved in S-Adenosylmethionine Antitumor Effects in Laryngeal Squamous Cancer Cells.Cancers · 2020Article
- Noninvasive Classification of Human Triple Negative Breast Cancer by PET Imaging with GRP78-Targeted Molecular Probe [Molecular imaging and biology · 2020Article
- Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function.International journal of molecular sciences · 2019Review
- Apoptosis and apoptotic body: disease message and therapeutic target potentials.Bioscience reports · 2019Review
- Combined effects of Lenvatinib and iodine-131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress.Experimental and therapeutic medicine · 2018Article
- Transcriptomic response of breast cancer cells to anacardic acid.Scientific reports · 2018Article
- Epoxyazadiradione suppresses breast tumor growth through mitochondrial depolarization and caspase-dependent apoptosis by targeting PI3K/Akt pathway.BMC cancer · 2018Article
- Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis.Cell stress & chaperones · 2017Article
- RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- ENDOPLASMIC RETICULUM STRESS IN SEPSIS.Shock (Augusta, Ga.) · 2015Review
- Identification of 5-nitrofuran-2-amide derivatives that induce apoptosis in triple negative breast cancer cells by activating C/EBP-homologous protein expression.Bioorganic & medicinal chemistry · 2015Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple negative breast cancers (TNBC) are among the most aggressive and therapy-resistant breast tumors and currently possess almost no molecular targets for therapeutic options in this horizon. In the present study we discerned the molecular mechanisms of potential interaction between the endoplasmic reticulum (ER) stress response and the MEK/ERK pathway in inducing apoptosis in TNBC cells. Here we observed that induction of ER stress alone was not sufficient to trigger significant apoptosis but simultaneous inhibition of the MEK/ERK pathway enhanced ER stress-induced apoptosis via a caspase-dependent mechanism. Our study also demonstrated nifetepimine, a dihydropyrimidone derivative as a potent anti-cancer agent in TNBC cells. Nifetepimine down-regulated the MEK/ERK pathway in MDAMB-231 and MDAMB-468 cells and resulted in blockage of ER stress-mediated GRP78 up-regulation. Detailed mechanistic studies also revealed that nifetepimine by down-regulating pERK expression also declined the promoter binding activity of TFII-I to the GRP78 promoter and in turn regulated GRP78 transcription. Studies further extended to in vivo Swiss albino and SCID mice models also revalidated the anti-carcinogenic property of nifetepimine. Thus our findings cumulatively suggest that nifetepimine couples two distinct signaling pathways to induce the apoptotic death cascade in TNBC cells and raises the possibility for the use of nifetepimine as a potent anti-cancer agent with strong immune-restoring properties for therapeutic intervention for this group of cancer bearers.
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