ArticleAmerican journal of cancer research2020
Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells.
Article in American journal of cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Importance of PERK pathway modulation on colorectal cancer management: a systematic review.BMC cancer · 2025Pooled it
- Antiproliferation and Anti-invasion Activity of Binuclear Copper(II) Complex in BRAFi-Resistant Melanoma Cells.ACS pharmacology & translational science · 2026Article
- Selective killing of ALT-cancer cells by Withaferin-A involves destabilization of Rad51 and disruption of DNA repair.Cell death & disease · 2026Article
- Exploring the therapeutic potential of withaferin A by modulating key oncosignaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Induction of Apoptosis and Activation of Endoplasmic Reticulum Stress by SJ6986 in Diffuse Large B-cell Lymphoma.Anti-cancer agents in medicinal chemistry · 2026Article
- Natural and Synthetic Compounds Against Colorectal Cancer: An Update of Preclinical Studies in Saudi Arabia.Current oncology (Toronto, Ont.) · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Iron Overloading Potentiates the Antitumor Activity of 5-Fluorouracil by Promoting Apoptosis and Ferroptosis in Colorectal Cancer Cells.Cell biochemistry and biophysics · 2024Article
- Modulating Endoplasmic Reticulum Stress in Gastrointestinal Cancers: Insights from Traditional Chinese Medicine.Pharmaceuticals (Basel, Switzerland) · 2024Review
- 4-O-Methylascochlorin Synergistically Enhances 5-Fluorouracil-Induced Apoptosis by Inhibiting the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer Cells.International journal of molecular sciences · 2024Article
- Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells.Frontiers in pharmacology · 2024Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum.Drug delivery · 2023Review
- Epigallocatechin-3-gallate and cancer: focus on the role of microRNAs.Cancer cell international · 2023Review
- Medicinal Characteristics ofPharmaceuticals (Basel, Switzerland) · 2023Review
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- Emerging roles of endoplasmic reticulum stress in the cellular plasticity of cancer cells.Frontiers in oncology · 2023Review
- Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance.Biomolecules & therapeutics · 2022Review
- Regulated cell death (RCD) in cancer: key pathways and targeted therapies.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of chemo-resistance against 5-fluorouracil (5-FU) in tumor cells is one of the main debacles in colorectal cancer (CRC) patients. A recent combination of 5-FU with oxaliplatin or cetuximab drastically improves the survival rate in CRC patients; however, the toxicity issue cannot be evaded completely. Thus, searching for novel drug combinations with high specificity and low toxicity is seemingly important. Owing to the less undesirable effects of natural products on normal cells, here we investigated the synergistic antitumor effect of withaferin-A (WA) in combination with 5-FU. Our results demonstrate that the combination of WA and 5-FU induces a significant antiproliferative effect and modulates endoplasmic reticulum (ER) stress in favor of cell death in colorectal cancer (CRC) cells. Mechanistically, the combination upregulates the expression of ER stress sensors (BiP, PERK, CHOP, ATF-4, and eIF2α) and executes PERK axis mediated apoptosis in CRC cells. Additionally, the combined treatment of WA and 5-FU mediated ER stress induces autophagy and apoptosis, which were confirmed by immunoblotting, acridine orange (AO) staining and annexin-V FITC by flow cytometry. In contrast, inhibition of ER stress with salubrinal significantly decreases both autophagic and apoptotic cell populations. Moreover, pharmacological inhibition of either autophagy or apoptosis by their respective inhibitors 3-methyladenine (3-MA) or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methyl ketone (Z-VAD-FMK) decreases their respective population of cells but could not affect either of the population significantly. Finally, the combination attenuates the expression of β-catenin pathway associated proteins and arrests cell cycle at the G
Indexed as
Identifiers
32266092PMC7136917W3015161809What OpenQuestion holds
Registered trials
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.