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>
Synergistic antitumor activity of vitamins C and K-3 on human urologic tumor cell lines
2-methyl-1; 4-naphthoquinone; bladder; cancer-chemotherapy; carcinoma cells; growth; isolated hepatocytes; l-ascorbic-acid; menadione; metabolism; mitomycin-c; oxidative stress; Pharmacology & Pharmacy; prostate; Research & Experimental Medicine; urologic neoplasms; vitamin C
A micro-tetrazolium assay was employed to evaluate vitamin C (VC), vitamin K-3 (VK3) and vitamin C/vitamin K-3 combinations (VC/VK3) for their antitumor activity against eight human urologic tumor cell lines. While the individual vitamins exhibited antitumor activity at high concentrations, co-administration of the vitamin in a VC : VK3 ratio of 100 : 1 potentiated antitumor activity 4- to 61-fold even when exposure times were as short as 1 hour. Administration of exogenous catalase destroyed the antitumor activity of the vitamins and suggested that catalase destroyed the antitumor activity of the vitamins and suggested that hydrogen peroxide and perhaps other reactive oxygen species were involved in the antitumor mechanism of these vitamins. Electron micrographs taken in a previous study demonstrated that vitamin treatment damaged mitochondria and may have impaired ATP synthesis. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis during the first five hours following a one hour VC/VK3 treatment, revealed: a transient increase in ATP production, a substantial decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that redox cycling of the vitamin combination increased oxidative stress until it surpassed the reducing ability of the cellular thiols and cellular or genetic damage ensured.
Venugopal M; Jamison J M; Gilloteaux J; Koch J A; Summers M; Giammar D; Sowick C; Summers J L
Life Sciences
1996
1996-09
Journal Article
<a href="http://doi.org/10.1016/0024-3205(96)00466-3" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(96)00466-3</a>
The additive effects of carnitine and ascorbic acid on distally burned dorsal skin flap in rats
ischemia; prevention; ultrastructure; Research & Experimental Medicine; model; metabolism; skeletal-muscle; vitamin C; burn; carnitine; skin flap; thermal-injury
Background: The purpose of this study was to determine the effects of combined use of L-carnitine and vitamin C on partially burned skin flap in an experimental rat model. Material/Methods: In the rat dorsal skin, a 10x3 cm flap was marked. The most distal 3x3 cm part was burned to full thickness. Twenty-four rats were randomized into four groups with 6 animals in each. Group 1 was simply followed tip. Group 2 was given 0.5 mg/kg vitamin C per day for 7 days, group 3 100 mg/kg carnitine per day for 7 days, and group 4 both carnitine and vitamin C. On the eighth postoperative day, the animals were sacrificed and examined. The surviving and necrotic areas were determined by macroscopic examination and measured with a planimeter. Results: The areas of flap necrosis were measured. The median surviving areas and areas of flap necrosis, respectively, of the groups were: group 1, 16.0 cm(2) and 14.0 cm(2); group 2, 18.25 cm(2) and 11.75 cm(2); group 3, 20.0 cm(2) and 10 cm(2); and group 4, 23.75 cm(2) and 6.25 cm(2). The surviving areas of the groups were found to be significantly different (p=0.000).
Arslan E; Basterzi Y; Aksoy A; Majka C; Unal S; Sari A; Demirkan F
Medical Science Monitor
2005
2005-06
Journal Article or Conference Abstract Publication
n/a
The in vitro antitumor activity of vitamins C and K-3 against ovarian carcinoma
alternative medicine use; aspects; autoschizis; cancer-chemotherapy; cell-lines; double-blind; k-3 combinations; mitomycin-c; Oncology; ovarian-cancer; phase-ii trial; pretreatment; tumor; ultrastructural; vitamin C; vitamin K-3
Background: The objective was to evaluate the cytotoxic effect and mechanism of action of vitamins C (VC) and K-3 (VK3) on ovarian carcinoma. Materials and Methods: Cytotoxicity assays were performed on ovarian cancer cell lines with VC, VK3 or a VC/VK3 combination. FIC index was employed to evaluate synergism. Flow cytometry was accomplished at 90% cytotoxic doses. Light, transmission electron microscopy and DNA isolation were performed. Results: Antitumor activity was exhibited by both VC, VK3 and VC/VK3. VC/VK3 demonstrated synergistic activity. VC/VK3 may induce a G(1) block in the cell cycle. Combined vitamin treatment resulted in cells that maintain apparently intact nuclei while extruding pieces of organelle-free cytoplasm. Degradation of chromosomal DNA was observed. Conclusion: Cell death (autoschizis) displayed characteristics of both apoptosis and necrosis. The cytotoxic effects observed may enable vitamins C and K-3 to play an adjuvant role in the treatment of ovarian cancer.
Von Gruenigen V E; Jamison J M; Gilloteaux J; Lorimer H E; Summers M; Pollard R R; Gwin C A; Summers J L
Anticancer Research
2003
2003-07
Journal Article
n/a