Potential therapeutic application of the association of vitamins C and K-3 in cancer treatment
oxidative stress; cancer; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; apoptosis; cell-death; growth-invitro; synergistic antitumor-activity; ascorbic-acid; carcinoma-cells; autoschizis; induced apoptosis; ascorbate (vitamin C); caloric restriction; cycle arrest; menadione (vitamin K-3); programmed; tumor-specific expression
The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K-3 in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K-3 administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK3-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K-3 as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.
Calderon P B; Cadrobbi J; Marques C; Hong-Ngoc N; Jamison J M; Gilloteaux J; Summers J L; Taper H S
Current Medicinal Chemistry
2002
2002-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.2174/0929867023368674" target="_blank" rel="noreferrer noopener">10.2174/0929867023368674</a>
The association of vitamins C and K-3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use coadjuvants in anticancer therapy
antitumor-activity; ascorbic-acid; autoschizis; cancer; chemotherapy; dna; factor-kappa-b; fragmentation; induced apoptosis; lines; oxidative stress; Pharmacology & Pharmacy; pretreatment; tumor-cells; vitamins C and K-3
`Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K-3 (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K-3, respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK3, they included: formation of H2O2 during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK3 may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K-3 into human clinics as a new, non-toxic adjuvant cancer therapy. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
Verrax J; Cadrobbi J; Delvaux M; Jamison J M; Gilloteaux J; Summers J L; Taper H S; Calderon P B
European Journal of Medicinal Chemistry
2003
2003-05
Journal Article
<a href="http://doi.org/10.1016/s0223-5234(03)00082-5" target="_blank" rel="noreferrer noopener">10.1016/s0223-5234(03)00082-5</a>
Inhibition of the development of metastases by dietary vitamin C : K-3 combination
ascorbate; ascorbic-acid; cancer-chemotherapy; growth-invitro; k-3 combinations; lung; lymph node; menadione; metastases; mouse liver; n-nitrosomorpholine; oxidative stress; Pharmacology & Pharmacy; prostatic-carcinoma cells; Research & Experimental Medicine; synergistic antitumor-activity; tumor; ultrastructural aspects; vitamin CK3
The tumor growth-inhibiting and chemo-potentiating effects of vitamin C and K(3)combinations have been demonstrated both in vitro and in vivo. The purpose of this study was to investigate the influence of orally administered vitamin C and K-3 on the metastasis of mouse liver tumor (T.L.T.) cells implanted in C3H mice. Adult male C3H mice were given water containing vitamin C and K3 (15 g/0.15 g dissolved in 1000 ml) beginning 2 weeks before tumor transplantation until the end of the experiment. T.L.T. cells (106) were implanted intramuscularly in the right thigh of mice. All mice were sacrificed 42 days after tumor transplantation. Primary tumor, lungs, lymph nodes and other organs or tissues suspected of harboring metastases were macroscopically examined. Samples of primary tumors, their local lymph nodes, lungs and main organs such as liver, kidneys, spleen were taken for histological examination. Forty-two percent of control mice exhibited lung metastases and 27% possessed metastases in local lymph nodes whereas 24% of vitamin-treated mice exhibited lung metastases and 10% possessed local lymph nodes metastases. The total number of lung metastases was 19 in control group and 10 in vitamin C and K-3-treated mice. Histopathological examination of the metastatic tumors from the vitamin-treated mice revealed the presence of many tumor cells undergoing autoschizic cell death. These results demonstrate that oral vitamin C and K3 significantly inhibited the metastases of T.L.T. tumors in C3H mice. At least a portion of this inhibition was due to tumor cell death by autoschizis. (C) 2004 Published by Elsevier Inc.
Taper H S; Jamison J M; Gilloteaux J; Summers J L; Calderon P B
Life Sciences
2004
2004-07
Journal Article
<a href="http://doi.org/10.1016/j.lfs.2004.02.011" target="_blank" rel="noreferrer noopener">10.1016/j.lfs.2004.02.011</a>