ArticleJournal of cellular physiology2010
Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways.
Article in Journal of cellular physiology, 2010. 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, 33 citations in OpenAlex.
- Targeting Reactive Species Stress and Nutrient Sensing to Enhance NK-Cell Function: Mechanistic Strategies for Overcoming Pancreatic Cancer Progression and Resistance Through Supplement Therapy.International journal of molecular sciences · 2026Review
- The anti-leukemic effects of vitamin K4 by modulating the JAK/STAT signaling pathway.Cancer cell international · 2026Article
- Vitamin K1 Induced Cytotoxic Effects and Transcriptomic Analysis in Jurkat T Lymphocyte Leukemia Cells.Cancer management and research · 2025Article
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- What Dietary Patterns and Nutrients are Associated with Pancreatic Cancer? Literature Review.Cancer management and research · 2023Review
- Vitamin K Contribution to DNA Damage-Advantage or Disadvantage? A Human Health Response.Nutrients · 2022Review
- Quercetin induces tongue squamous cell carcinoma cell apoptosis via the JNK activation-regulated ERK/GSK-3α/β-mediated mitochondria-dependent apoptotic signaling pathway.Oncology letters · 2022Article
- Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity.Cell death & disease · 2021Article
- G2M checkpoint pathway alone is associated with drug response and survival among cell proliferation-related pathways in pancreatic cancer.American journal of cancer research · 2021Article
- 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
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- Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.Advances in nutrition (Bethesda, Md.) · 2015Review
- Vitamin K1 exerts antiproliferative effects and induces apoptosis in three differently graded human colon cancer cell lines.BioMed research international · 2015Article
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- A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells, associated with activation of JNK/AP-1 signaling.Cancer biology & therapy · 2013Article
- Sorafenib sensitizes hepatocellular carcinoma cells to physiological apoptotic stimuli.Journal of cellular physiology · 2012Article
- Metabolic Profiling Comparison of Human Pancreatic Ductal Epithelial Cells and Three Pancreatic Cancer Cell Lines using NMR Based Metabonomics.Journal of molecular biomarkers & diagnosis · 2012Article
- Resveratrol mobilizes Ca2+ from intracellular stores and induces c-Jun N-terminal kinase activation in tumoral AR42J cells.Molecular and cellular biochemistry · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Apoptosis has been shown to be induced by many agents, including the clinically useful Sorafenib and K vitamins (VKs). Since few agents have activity against pancreas cancer cell growth, we evaluated the role of naturally occurring K vitamins and Sorafenib both independently and together on the growth in culture of pancreas adenocarcinoma cell lines, including PL-5, PANC-1, and MIA PaCa-2. We found that when a K vitamin was combined with Sorafenib, the dose of Sorafenib required for growth inhibition was substantially reduced. Furthermore, growth could be inhibited at doses of each VK plus Sorafenib in combination that were ineffective when used alone. This effect was seen using vitamins K1, K2, and K5. The combination of VK1 plus Sorafenib-induced apoptosis, as determined by both FACS and TUNEL staining. Phospho-ERK and Bcl-2 levels were decreased, but not levels of other bcl-2 family members. Cleavage of caspases 3 and 8, PARP and Bid were all induced by this combination. Vitamin K1 plus Sorafenib combination also resulted in elevated levels of activated c-Jun N-terminal kinase (JNK) and its substrates c-Jun and FasL. JNK inhibition partly antagonized the induction of apoptosis. Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in pancreas cancer cells, involving both inhibition of the RAF/MEK/ERK pathway as well as activation of the JNK, c-Jun and FasL apoptotic pathway. Since both agents are available for human use, the combination is attractive for evaluation against pancreas cancer growth in vivo.
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