ArticleBMC cancer2016
Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- Unraveling the Peculiar Features of Mitochondrial Metabolism and Dynamics in Prostate Cancer.Cancers · 2023Review
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- Silybin induces endothelium-dependent vasodilation via TRPV4 channels in mouse mesenteric arteries.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Article
- Silver nanoparticle-induced alteration of mitochondrial and ER homeostasis affects human breast cancer cell fate.Toxicology reports · 2022Article
- ROS and Endoplasmic Reticulum Stress in Pulmonary Disease.Frontiers in pharmacology · 2022Review
- Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.Parasites & vectors · 2021Article
- JI017, a Complex Herbal Medication, Induces Apoptosis via the Nox4-PERK-CHOP Axis in Ovarian Cancer Cells.International journal of molecular sciences · 2021Article
- Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets.Cells · 2020Review
- Observational
- NOX2-Derived Reactive Oxygen Species in Cancer.Oxidative medicine and cellular longevity · 2020Review
- Quantitative proteomic analysis reveals AK2 as potential biomarker for late normal tissue radiotoxicity.Radiation oncology (London, England) · 2019Article
- Diosmetin induces apoptosis and enhances the chemotherapeutic efficacy of paclitaxel in non-small cell lung cancer cells via Nrf2 inhibition.British journal of pharmacology · 2019Article
- Silibinin sensitizes TRAIL-mediated apoptosis by upregulating DR5 through ROS-induced endoplasmic reticulum stress-CaOncotarget · 2018Article
- The novel resveratrol derivative 3,5-diethoxy-3',4'-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro.Acta pharmacologica Sinica · 2017Article
- Article
- Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Oxidative medicine and cellular longevity · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSilibinin, a biologically active compound of milk thistle, has chemopreventive effects on cancer cell lines. Recently it was reported that silibinin inhibited tumor growth through activation of the apoptotic signaling pathway. Although various evidences showed multiple signaling pathways of silibinin in apoptosis, there were no reports to address the clear mechanism of ROS-mediated pathway in prostate cancer PC-3 cells. Several studies suggested that reactive oxygen species (ROS) play an important role in various signaling cascades, but the primary source of ROS was currently unclear.
methodsThe effect of silibinin was investigated on cell growth of prostate cell lines by MTT assay. We examined whether silibinin induced apoptosis through production of ROS using flow cytometry. Expression of apoptosis-, endoplasmic reticulum (ER)-related protein and gene were determined by western blotting and RT-PCR, respectively.
resultsResults showed that silibinin triggered mitochondrial ROS production through NOX4 expression and finally led to induce apoptosis. In addition, mitochondrial ROS caused ER stress through disruption of Ca(2+) homeostasis. Co-treatment of ROS inhibitor reduced the silibinin-induced apoptosis through the inhibition of NOX4 expression, resulting in reduction of both Ca(2+) level and ER stress response.
conclusionsTaken together, silibinin induced mitochondrial ROS-dependent apoptosis through NOX4, which is associated with disruption of Ca(2+) homeostasis and ER stress response. Therefore, the regulation of NOX4, mitochondrial ROS producer, could be a potential target for the treatment of prostate cancer.
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