The utility of vitamin K3 for local injection therapy against advanced pancreas cancer
Abstract number: 1733_1445
Osada S., Komori S., Matsui S., Tokuyama Y., Sakashita F.
Background: The molecular mechanism of Vitamin K3 (VK3)-induced cellular growth inhibitory effect was characterised to evaluate its efficacy by local injection for application against unresectable pancreatic cancer.
Methods: Cell viability was determined by test method with MTT. Expressions of cellular proteins were evaluated by Western blott analysis.
Results: The IC50 of VK3 for pancreas cancer cells was calculated to be 42.1 ± 3.5 microM. By Western blot analysis, VK3 was shown to induce phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 minutes. Expression of apoptosis by VK3, as shown by caspase-3 activation, and poly ADP-ribose polymerase cleavage is found. Treatment with the thiol-antioxidant (>0.2 mM) completely abrogated VK3-induced ERK but not JNK phosphorylation or inhibition of proliferation. A caspase-3 inhibitor had no inhibitory effect on the proliferative activity of VK3. As a comparison with agent to mediate cellular molecular phosphorylation, oxidative stress (H2O2) at concentrations >5.0 mM was found to inhibit cell proliferation at 24 hours. H2O2 also induced phosphorylation of JNK or ERK, and activation of Caspase-3. And H2O2-induced these activations were completely abrogated by non-thiol-antioxidant, but not thiol-antioxidant. Because H2O2 mediated growth inhibitory effect was quite hasty, high toxicity was anxious for in vivo study. By contrast, VK3 was found to induce extensive tumour tissue necrosis. By Western blot, ERK phosphorylation, but not JNK, was clearly detected only in response to VK3 injection into tumour tissue.
Conclusion: The local injection with VK3 may be useful in the curative treatment of unresectable tumours, and the detection of ERK phosphorylation in tissue is important to predict the effect.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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