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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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Boucher, R., Germain, H., & Desgagné-Penix, I. (2025) · Plants · doi:10.3390/plants14091372 · Cited by 23
Anticancer and chemosensitizing activities of stilbenoids from three orchid species
Sein, K. L., Lertnitikul, N., Suttisri, R., & Jianmongkol, S. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02352-x · Cited by 13
Self-citationBakrim, S., Elouafy, Y., Touhtouh, J., Aanniz, T., El Kadri, K., Khalid, A., Fawzy, S., Mesaik, M. A., Lee, L.-H., Chamkhi, I., et al. (2024) · Fitoterapia · doi:10.1016/j.fitote.2024.106182 · Cited by 12
Bolat, M., Çelebi, F., Şengül, E., Çınar, İ., Yıldırım, S., & Bolat, İ. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04269-7 · Cited by 10
Kołodziejczyk-Czepas, J. (2024) · Foods · doi:10.3390/foods13071118 · Cited by 7
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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- This page
- CoChat. (2026). Citation check: N-Trans-p-Coumaroyltyramine Enhances Indomethacin- and Diclofenac-induced Apoptosis Through Endoplasmic Reticulum Stress-dependent Mechanism in MCF-7 Cells. https://app.cochat.ai/papers/10.21873/anticanres.15659
- The paper
- WONGSAKUL, A., LERTNITIKUL, N., SUTTISRI, R., & JIANMONGKOL, S. (2022). N-Trans-p-Coumaroyltyramine Enhances Indomethacin- and Diclofenac-induced Apoptosis Through Endoplasmic Reticulum Stress-dependent Mechanism in MCF-7 Cells. Anticancer Research. https://doi.org/10.21873/anticanres.15659
