The in vitro and in vivo Antitumor Activity of Vitamin C: K3 Combinations Against Prostate Cancer

Abstract

Organic chemistry Z 0200The in vitro and in vivo Antitumor Activity of Vitamin C: K3 Combinations Against Prostate Cancer -[191 refs.]. -(JAMISON, J. M.; GILLOTEAUX, J.; TAPER, H. S.; CALDERON, P. B.; PERLAKY, L.; THIRY, M.; NEAL, D. R.; BLANK, J. L.; CLEMENTS, R. J.; GETCH, S.; et al.; Horizons Cancer Res. 7 (2005) 189-236; Dep. Urol., Summa Health Syst., Northeastern Ohio Univ., Akron, OH 44325, USA; Eng.) -Lindner 16-260

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

“…Electrophoresis of DNA revealed a spread pattern. These results in conjunction with previous studies (Buc Calderon et al, 2003;Verrax et al, 2003Verrax et al, , 2004Jamison et al, 2005) suggested that Ca 2ϩ disregulation and cell acidification led to the caspase-3-independent serial reactivation of DNase I and DNase II and the degradation of T24 cell DNA ).…”

“…The few mitochondria observed distally, near the self-excision zone, were only swollen. In summary, menadione-induced actions are rapid and involve depletion of reduced thiols, Ca 2ϩ disregulation, and caspase-3-independent reactivation of DNase I within the first hour of treatment Jamison et al, 2005). This subsequent DNA degradation is consistent with the decreased optical density of Feulgen staining (Fig.…”

“…VC exhibits selective toxicity toward melanoma (Bram et al, 1980), leukemia (Park et al, 1980), neuroblastoma (Prasad et al, 1979b), and ascite (Liotti et al, 1984) cell lines by inhibiting cancer cell growth in vitro (Benade et al, 1969;Yamafuji et al, 1971;Koch and Biaglow, 1978;De Loecker et al, 1993;Leung et al, 1993;Medina et al, 1994;Gilloteaux et al, 1995Gilloteaux et al, , 1998aGilloteaux et al, , 1998bGilloteaux et al, , 2001aGilloteaux et al, , 2001bGilloteaux et al, , 2001cGilloteaux et al, , 2003aGilloteaux et al, , 2003bGilloteaux et al, , 2004Gilloteaux et al, , 2005Jamison et al, 1996Jamison et al, , 2002Jamison et al, , 2004Jamison et al, , 2005Menon et al, 1998). VC is selectively toxic to tumor cells in vivo (Pierson and Meadows, 1983;Varga and Airoldi, 1983;Tsao et al, 1988;Taper et al, 2001) and can kill cells in solid primary tumors and metastases (Taper et al, 1987(Taper et al, , 1996Taper and Roberfroid, 1992).…”

“…VK 3 has also been shown to be cytotoxic to a variety of urological tumors (Venugopal et al, 1996a(Venugopal et al, , 1996bErvin et al, 1998;Gilloteaux et al, 1998aGilloteaux et al, , 1998bGilloteaux et al, , 1999aGilloteaux et al, , 2001aGilloteaux et al, , 2001bGilloteaux et al, , 2001cGilloteaux et al, , 2005Jamison et al, 2004Jamison et al, , 2005. Furthermore, VK 3 has been shown to be equally potent against human multiple drug-resistant and drug-sensitive cells, as well as against human tumor explants derived from patients who are refractory to other types of chemotherapy .…”

“…The single-electron reduction of the quinone produces the semiquinone that reduces oxygen to the superoxide radical and regenerates the quinone. As a result, redox cycling can ensue and produce large amounts of superoxide, which can dismutate to form H 2 O 2 or form more toxic ROS via intracellular metal-catalyzed reactions (O'Brien, 1991;Venugopal et al, 1996aVenugopal et al, , 1996bJamison et al, 2001Jamison et al, , 2002Jamison et al, , 2004. This redox cycling generates oxidative stress (Bellomo et al, 1982;Cohen and Slubberfield, 1990) and results in a number of deleterious effects on T24 cells, including depletion of NADPH (Akman et al, 1985) and reduced glutathione (Carbonera and Azzone, 1988;Bellomo et al, 1990;Cohen and Stubberfield, 1990;Fawthrop et al, 1991) with the oxidation of sulfhydryl groups in proteins, especially microtubules and other cytoskeletal proteins, such as the cytokeratins (Bellomo et al, 1990;Malorni et al, 1991;Wu et al, 1993aWu et al, , 1993bJarabak and Jarabak, 1995).…”