ArticleAntioxidants (Basel, Switzerland)2025
Piperine Induces Apoptosis and Cell Cycle Arrest via Multiple Oxidative Stress Mechanisms and Regulation of PI3K/Akt and MAPK Signaling in Colorectal Cancer Cells.
Article in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Recent advances in piperine and its derivatives as potential anticancer agents.RSC medicinal chemistry · 2026Review
- Mannose-Functionalized Chitosan-TPGS/Tween 80 Nanocarriers for Macrophage Targeting: Enhanced Piperine Delivery to Potentiate Anti-Inflammatory and Antioxidant Therapy.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanistic Insights into Piperine-Driven Oxidative Stress, Autophagy Activation and Anti-Migration Effects in Caco-2 Cells.Molecules (Basel, Switzerland) · 2026Article
- Piperine-induced AMPK activation and cell cycle arrest: insights from molecular simulations and experimental validation in breast cancer.Medical oncology (Northwood, London, England) · 2026Article
- Biosynthesis of Silver Nanoparticles Using Black Pepper (Piper nigrum) Seed Extract and Evaluation of Their Cytotoxicity.Chemistry & biodiversity · 2026Article
- Repurposing natural compounds: computational evaluation ofFrontiers in bioinformatics · 2026Article
- Piperine and Tabersonine, but Not Lupinine, InhibitInternational journal of molecular sciences · 2025Article
- Comparative Ultrasonic Bath and Probe Extraction of Piperine fromBiomolecules · 2025Article
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- Pathogenesis of Cutaneous Mycobacterial Infections-International journal of molecular sciences · 2025Review
- Article
- Effects of high-altitude environments on intervertebral disc degeneration and transcriptome profiling of the nucleus pulposus.Frontiers in cell and developmental biology · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
Piperine, a phytochemical alkaloid, exhibits notable anticancer properties in several cancer cell types. In this study, we investigated the mechanisms by which piperine induces cell death and apoptosis in colorectal cancer (CRC) cells, focusing on oxidative stress and key signaling pathways. Using MTT assay, flow cytometry, gene overexpression, and Western blot analysis, we observed that piperine significantly reduced cell viability, triggered G1 phase cell cycle arrest, and promoted apoptosis in DLD-1 cells. In addition, piperine effectively suppressed cell viability and induced apoptosis in other CRC cell lines, including SW480, HT-29, and Caco-2 cells. These effects were associated with increased intracellular reactive oxygen species (ROS) generation, mediated by the regulation of mitochondrial complex III, NADPH oxidase, and xanthine oxidase. Additionally, piperine modulated signaling pathways by inhibiting phosphoinositide 3-kinase (PI3K)/Akt, activating p38 and p-extracellular signal-regulated kinase (ERK). Pretreatment with antimycin A, apocynin, allopurinol, and PD98059, and the overexpression of p-Akt significantly recovered cell viability and reduced apoptosis, confirming the involvement of these pathways. This study is the first to demonstrate piperine induces apoptosis in CRC cells through a multifaceted oxidative stress mechanism and by critically modulating PI3K/Akt and ERK signaling pathways.
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