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>
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
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