ArticleInternational journal of cancer2010
Vitamin K enhancement of sorafenib-mediated HCC cell growth inhibition in vitro and in vivo.
Article in International journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study.Cancer medicine · 2021Trial
- Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines.Digestive diseases and sciences · 2011Trial
- Ferritinophagy induced ferroptosis in the management of cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Vitamin K Contribution to DNA Damage-Advantage or Disadvantage? A Human Health Response.Nutrients · 2022Review
- New insights into vitamin K biology with relevance to cancer.Trends in molecular medicine · 2022Review
- Medicinal Prospects of Antioxidants From Algal Sources in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Sorafenib and Mesenchymal Stem Cell Therapy: A Promising Approach for Treatment of HCC.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Strong enhancement by IGF1-R antagonists of hepatocellular carcinoma cell migration inhibition by Sorafenib and/or vitamin K1.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- IGF-1R tyrosine kinase inhibitors and Vitamin K1 enhance the antitumor effects of Regorafenib in HCC cell lines.Oncotarget · 2017Article
- Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment.Cancer science · 2017Article
- Article
- Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma.Journal of Cancer · 2017Article
- Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways.PloS one · 2016Article
- Vitamin K and hepatocellular carcinoma: The basic and clinic.World journal of clinical cases · 2015Review
- Vitamin K1 exerts antiproliferative effects and induces apoptosis in three differently graded human colon cancer cell lines.BioMed research international · 2015Article
- ABT-263 enhances sorafenib-induced apoptosis associated with Akt activity and the expression of Bax and p21((CIP1/WAF1)) in human cancer cells.British journal of pharmacology · 2014Article
- Early prediction of response of sorafenib on hepatocellular carcinoma by CT perfusion imaging: an animal study.The British journal of radiology · 2014Article
- YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma.Molecular cancer · 2014Article
- Reversibility of regorafenib effects in hepatocellular carcinoma cells.Cancer chemotherapy and pharmacology · 2013Article
- Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro.Journal of cellular physiology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The multikinase inhibitor sorafenib is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including sorafenib as well as by the naturally occurring K vitamins (VKs). As few nontoxic agents have activity against HCC growth, we evaluated the activity of sorafenib and VKs, both independently and together on the growth of HCC cells in vitro and in vivo. We found that when VK was combined with sorafenib, the concentration of sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus sorafenib that were ineffective with either agent alone, using vitamins K1, K2 and K5. Combination of VK1 plus sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho-extracellular signal-regulated kinase (ERK) levels were decreased as was myeloid cell leukemia sequence 1 (Mcl-1), an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At subeffective sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho-ERK and Mcl-1 staining. Thus, combination of VK1 plus sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/mitogen-activated protein kinase kinase/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf: sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. As both agents are available for human use, the combination has potential for improving sorafenib effects in HCC.
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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.