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N-Trans-p-Coumaroyltyramine Enhances Indomethacin- and Diclofenac-induced Apoptosis Through Endoplasmic Reticulum Stress-dependent Mechanism in MCF-7 Cells
Abstract
BACKGROUND/AIM: The anticancer potential of indomethacin and diclofenac has been reported against several types of cancer cells. In this study, we investigated the enhancement effect of a coumaric acid derivative found in some Piper plants, N-trans-p-coumaroyltyramine (TCT) on indomethacin and diclofenac cytotoxicity in breast cancer cells. MATERIALS AND METHODS: MCF-7 and mitoxantrone-resistant MCF-7 (MCF-7/MX) cancer cells were treated with indomethacin or diclofenac in the presence of TCT for 48 h. Cell viability, apoptosis, mitochondrial function and signaling proteins were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Hoechst 33342, tetramethyl-rhodamine-ethyl-ester and western blot analysis, respectively. RESULTS: Combination treatment resulted in significant reduction of cell viability and mitochondrial membrane potential, whereas the ratio of BCL2-associated X, apoptosis regulator to BCL2 apoptosis regulator, and apoptosis increased. The enhancing effect of TCT was related to reduced nuclear factor-erythroid factor 2-related factor 2/heme oxygenase-1 expression, and increased activation of the protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha/activating transcription factor 4/C/EBP homologous protein signaling pathways. CONCLUSION: TCT in combination with indomethacin or diclofenac promoted endoplasmic reticulum stress-dependent apoptosis in breast cancer cells.
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In the citing paper
“Exposure to 100 μM of N-p-trans-coumaroyltyramine for 48 h decreased MCF-7 viability by more than twofold when combined with 10 μM of both indomethacin and diclofenac [69].”
In the citing paper
“Furthermore, 100 μM of N-p-trans-coumaroyltyramine increased the cytotoxic activity of endoplasmic reticulum stressors, such as thapsigargin (0.0125 μM), tunicamycin (0.3 μM), rotenone (1.0 μM), and hydrogen peroxide (10 μM) in both MCF-7 cell lines [69].”
In the citing paper
“For MCF-7/MX cells, 100 μM of N-p-trans-coumaroyltyramine decreased cell viability by twofold for 10 μM of indomethacin and 1.5-fold for diclofenac.”
In the citing paper
“N-p-trans-coumaroyltyramine was shown to enhance the sensitivity of indomethacin and diclofenac, two nonsteroidal anti-inflammatory drugs with antiproliferative activity against certain cancer types, in MCF-7 (breast cancer) and mitoxantrone-resistant MCF-7 (MCF-7/MX) cell lines.”
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Self-citationda Silva, N. P., Valle, A. B. C. D. S., de Oliveira, L. C. A., Aleixo, D. T., Chellini, P. R., Sant’Ana, A. C., Cuin, A., Moya, S. E., Tavares, G. D., & Pittella, F. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108644
Zhou, X., Wu, D., Zhang, X., & Zhang, X. (2026) · Medicine · doi:10.1097/md.0000000000050440
Metadata
- Authors
- WONGSAKUL, A., LERTNITIKUL, N., SUTTISRI, R., & JIANMONGKOL, S.
- Affiliations
- Chulalongkorn University (TH)
- Venue
- Anticancer Research
- Published
- 2022-03-28
- Volume
- 42
- Issue
- 4
- Pages
- 1833-1844
- ISSN
- 0250-7005 (ISSN-L)
- 1791-7530
- OpenAlex
- W4220877179
- Cited by
- 11
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anticancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Piperaceae Chemical and Biological Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- indomethacin, diclofenac, endoplasmic reticulum stress, apoptosis, breast cancer, MCF-7 cells, mitoxantrone resistance, coumaric acid derivatives, Piper, combination therapy, mitochondrial membrane potential, Bax/Bcl-2 ratio
- MeSH terms
- Coumaric Acids, Diclofenac, Humans, Indomethacin, Apoptosis, Endoplasmic Reticulum Stress, MCF-7 Cells
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