Scanning Electron-microscopy And Transmission Electron-microscopy Aspects Of Synergistic Antitumor-activity Of Vitamin-c Vitamin K-3 Combinations Against Human Prostatic-carcinoma Cells
cancer-chemotherapy; cultured-mammalian-cells; cytoskeleton; cytotoxicity; growth-invitro; induced oxidative stress; isolated hepatocytes; l-ascorbic-acid; lines; menadione; Microscopy; prostate carcinoma; ruthenium tetroxide; toxicity; ultrastructure; vitamin-c; vitamin-k-3
Gilloteaux J; Jamison J M; Venugopal M; Giammar D; Summers J L
Scanning Microscopy
1995
1995-03
Journal Article or Conference Abstract Publication
n/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>
In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K-3 combination
apoptosis; cancer; cancer-chemotherapy; carcinoma cells; Cell Biology; cell death; deoxyribonuclease-ii; DNASE; growth-invitro; identification; lines; necrobiology; pretreatment; programmed cell-death; Prostate cancer; synergistic antitumor-activity; vitamin C; vitamin K-3
Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K-3 combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-mum sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles.
Taper H S; Jamison J M; Gilloteaux J; Gwin C A; Gordon T; Summers J L
Journal of Histochemistry & Cytochemistry
2001
2001-01
Journal Article
<a href="http://doi.org/10.1177/002215540104900111" target="_blank" rel="noreferrer noopener">10.1177/002215540104900111</a>