ArticleCellular oncology (Dordrecht, Netherlands)2019
Piperlongumine potentiates the antitumor efficacy of oxaliplatin through ROS induction in gastric cancer cells.
Article in Cellular oncology (Dordrecht, Netherlands), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy.Frontiers in oncology · 2022Pooled it
- Neferine-Targeted Inhibition of TrxR1 Triggers Apoptosis Through Disrupting Redox Homeostasis in Pancreatic Cancer Cells.Molecular carcinogenesis · 2026Article
- Piperlongumine Inhibits Malignant Progression of Esophageal Squamous Cells Through the PI3K/AKT Signaling Pathway.Biochemical genetics · 2026Article
- The Efficiency of Plant Extracts in the Prevention of Gastric Cancer: A Systematic Review.Health science reports · 2025Review
- Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover.JCI insight · 2025Article
- Herbs and their Active Constituents for Gastric Cancer and Related Problems - Preclinical and Clinical Studies.Current protein & peptide science · 2025Review
- Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance.Chinese medicine · 2024Review
- Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells.International journal of biological sciences · 2024Article
- Molecular mechanisms of ferroptosis and its antitumor applications in natural products.Acta biochimica et biophysica Sinica · 2023Review
- Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence.Antioxidants (Basel, Switzerland) · 2023Review
- Piperlongumine Induces Cellular Apoptosis and Autophagy via the ROS/Akt Signaling Pathway in Human Follicular Thyroid Cancer Cells.International journal of molecular sciences · 2023Article
- Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin.World journal of gastrointestinal oncology · 2023Article
- An Evaluation of Fluorouracil plus Paclitaxel and Oxiliplatin as a First-Line Treatment for Advanced Gastric Squamous Cell Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Article
- Anticancer applications of phytochemicals in gastric cancer: Effects and molecular mechanism.Frontiers in pharmacology · 2022Review
- The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance.Frontiers in molecular biosciences · 2022Review
- Constructing a novel gene signature derived from oxidative stress specific subtypes for predicting survival in stomach adenocarcinoma.Frontiers in immunology · 2022Article
- Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Antioxidant stress and anticancer activity of peptide‑chelated seleniumInternational journal of molecular medicine · 2021Article
- Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
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10 authors at 1 institution in 1 country.
Funding
Abstract
purposeOxaliplatin is one of the most commonly used chemotherapeutic agents in the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Therefore, there is a pressing need to develop novel therapies to potentiate the efficacy and reduce the toxicity of oxaliplatin. Piperlongumine (PL), an alkaloid isolated from Piper longum L., has recently been identified as a potent agent against cancer cells in vitro and in vivo. In the present study, we investigated whether PL can potentiate the antitumor effect of oxaliplatin in gastric cancer cells.
methodsCellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells or tumor tissues was determined using an endpoint insulin reduction assay. Western blotting was used to analyze the expression levels of the indicated proteins. Nude mice xenograft models were used to test the effects of PL and oxaliplatin combinations on gastric cancer cell growth in vivo.
resultsWe found that PL significantly enhanced oxaliplatin-induced growth inhibition in both gastric and colon cancer cells. Moreover, we found that PL potentiated the antitumor effect of oxaliplatin by inhibiting TrxR1 activity. PL combined with oxaliplatin markedly suppressed the activity of TrxR1, resulting in the accumulation of ROS and, thereby, DNA damage induction and p38 and JNK signaling pathway activation. Pretreatment with antioxidant N-acetyl-L-cysteine (NAC) significantly abrogated the combined treatment-induced ROS generation, DNA damage and apoptosis. Importantly, we found that activation of the p38 and JNK signaling pathways prompted by PL and oxaliplatin was also reversed by NAC pretreatment. In vivo, we found that PL combined with oxaliplatin significantly suppressed tumor growth in a gastric cancer xenograft model, and effectively reduced the activity of TrxR1 in tumor tissues. Remarkably, we found that PL attenuated body weight loss evoked by oxaliplatin treatment.
conclusionsOur data support a synergistic effect of PL and oxaliplatin and suggest that application of its combination may be more effective for the treatment of gastric cancer than oxaliplatin alone.
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