Naturally occurring K vitamins inhibit pancreatic cancer cell survival through a caspase-dependent pathway

Journal of Gastroenterology and Hepatology
Shayna L ShowalterBrian I Carr

Abstract

Available medical therapies against pancreatic cancer are largely ineffective and have many side-effects. Physiologically, vitamins K1 and K2 (VK) act as co-factors for gamma-carboxylation of prothrombin and other coagulation factors. In previous studies, VK analogs have been found to have potent negative effects on the survival of various cancer cells. We hypothesized that the well-tolerated and naturally occurring VK1 and VK2 may be used to inhibit pancreatic cancer cell survival. Four pancreas cancer cell lines were tested. Two of these (MiaPaCa2 and PL5) were found to be sensitive to VK1 and VK2 (IC50 values < or =150 microM). To address the mechanisms of this effect on cell survival, we performed cell cycle and apoptosis studies using VK2 (the more potent compound). We found that VK induced caspase-dependent apoptosis in over 60% of cells in the sensitive lines at the half maximal inhibitory concentration (IC(50)) range. Further, this induction in apoptosis was antagonized by a caspase inhibitor. Accompanying apoptosis, a dose- and time-dependent induction of extracellular signal-regulated kinase (ERK) phosphorylation occurred when sensitive lines were treated with either VK1 or VK2 at inhibitory doses. Simultaneous co-tre...Continue Reading

References

Jan 1, 1988·Annual Review of Nutrition·P A Price
May 20, 1988·Cell·B Furie, B C Furie
Jan 1, 1980·CRC Critical Reviews in Biochemistry·J W Suttie
Nov 24, 1995·The Journal of Biological Chemistry·Y NishikawaS Naganathan
Sep 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Z WangB I Carr
Feb 15, 1997·The Journal of Clinical Investigation·S P SaxenaL G Israels
Nov 10, 1998·Critical Reviews in Eukaryotic Gene Expression·C M ShanahanP L Weissberg
May 12, 2000·Hematology/oncology Clinics of North America·C Vermeer, L J Schurgers
Mar 19, 2004·The New England Journal of Medicine·John P NeoptolemosUNKNOWN European Study Group for Pancreatic Cancer
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Motoyuki OtsukaMasao Omata
May 27, 2006·Critical Reviews in Oncology/hematology·Andrea MancusoCora N Sternberg
Nov 8, 2006·International Journal of Oncology·Kazuya MatsumotoYoshikazu Murawaki
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Iwata OzakiKyosuke Yamamoto
Apr 1, 2008·Vitamins and Hormones·Toshihiko Mizuta, Iwata Ozaki

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Citations

Jun 6, 2015·International Journal of Oncology·Michele LinsalataFrancesco Russo
Sep 17, 2017·Oncotarget·Subramanyam DasariGnanasekar Munirathinam
Nov 15, 2015·Advances in Nutrition·Ashley H Davis-Yadley, Mokenge P Malafa
Feb 23, 2019·International Journal of Molecular Sciences·Maurice HalderLeon Schurgers
Jul 13, 2017·Journal of Nutrition and Metabolism·Gerry Kurt Schwalfenberg

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