ArticleJournal of cancer research and clinical oncology2008
Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei.
Article in Journal of cancer research and clinical oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Disproportionality Analysis of Breast Cancer-Related Reports Across Vitamin K Homologs in the FDA Adverse Event Reporting System.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.Nature aging · 2026Article
- Calumenin, A Calcium-Binding Modulatory Protein, Effective in Pathological Calcifications and Cancers, With Therapeutic Application Promise.FASEB bioAdvances · 2025Review
- Article
- Nuclear receptors in ovarian cancer: changing paradigms in cancer therapeutics.Frontiers in oncology · 2024Review
- Vitamin K Contribution to DNA Damage-Advantage or Disadvantage? A Human Health Response.Nutrients · 2022Review
- Role of Vitamin K in Selected Malignant Neoplasms in Women.Nutrients · 2022Review
- Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities.Frontiers in pharmacology · 2022Review
- Role of emerging vitamin K‑dependent proteins: Growth arrest‑specific protein 6, Gla‑rich protein and periostin (Review).International journal of molecular medicine · 2021Review
- Vitamins and Uterine Fibroids: Current Data on Pathophysiology and Possible Clinical Relevance.International journal of molecular sciences · 2020Review
- Retracted Article: The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction.RSC advances · 2019Article
- Research progress on the anticancer effects of vitamin K2.Oncology letters · 2018Review
- Review
- Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia.Molecular bioSystems · 2015Article
- TR3 modulates platinum resistance in ovarian cancer.Cancer research · 2013Article
- Article
- Vitamin k2, a naturally occurring menaquinone, exerts therapeutic effects on both hormone-dependent and hormone-independent prostate cancer cells.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway.Molecular and cellular biochemistry · 2010Article
- Orphan nuclear receptor Nur77 is required for the differentiation of C6 glioma cells induced by cholera toxin.Acta pharmacologica Sinica · 2009Article
- Down-regulation of NR4A1 in follicular thyroid carcinomas is restored following lithium treatment.Clinical endocrinology · 2009Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe examined the growth-inhibitory and apoptosis-inducing effects of vitamin K(2) (VK(2); menaquinone-4) on various lines of human ovarian cancer cells to study the mechanism of induction of apoptosis by VK(2).
methodsCell proliferation was determined by XTT method, and apoptotic cells were detected by Hoechst staining. TR3, also known as Nur77 and NGFI-B, was detected by immunoblotting and immunofluorescence analysis. Role of TR3 on induction of apoptosis was examined by a siRNA experiment. RESULTS AND
conclusionsWe found that PA-1 cells were the most sensitive to VK(2) (IC(50) = 5.0 +/- 0.7 microM), while SK-OV-3 cells were resistant to VK(2). Immunoblotting and immunofluorescence analyses indicated that levels of TR3 were elevated in cell lysates 48 h after the start of treatment with 30 microM VK(2). In the VK(2)-treated cells, TR3 accumulated at significant levels in mitochondria, as well as in the nuclei of PA-1 cells. No similar changes were observed in SK-OV-3 cells under the same conditions. Treatment of PA-1 cells with small interfering RNA (siRNA) directed against TR3, and with cycloheximide or SP600125 (an inhibitor of c-jun N-terminal kinase; JNK), separately, inhibited the VK(2)-induced synthesis of TR3 and apoptosis. From these results, we can conclude that an increase in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nuclei might be involved in the induction of apoptosis by VK(2) and that the synthesis of TR3 might be regulated through a JNK signaling pathway.
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