Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-L-ascorbate.
We investigated whether the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) is mediated via oxidation-involved mechanism, in three different systems: 3'-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular carcinoma (in vivo), its homogenate (semi in vivo), and cultured cells (in vitro). Oral intake of DAB irreversibly produced hepatocellular carcinoma in rats, with a maximum incidence of carcinogenesis after 4 months. Intravenous administration of SBA induced vacuolar, eosinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2-CL) in the cancerous tissue than in the normal tissue. When SBA was directly added to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPMI1640 medium supplemented with 10% fetal bovine serum, methionine was oxidized to methionine sulfoxide and H2O2 was produced in amounts that sufficiently induce apoptotic cell death in human promyelocytic leukemic HL-60 cells. Cytotoxic activity of SBA was significantly reduced by catalase. These data suggest that antitumor activity of SBA in vivo might at least in part be due to H2O2, produced from SBA.
Asano
K
K
Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
Satoh
K
K
Hosaka
M
M
Arakawa
H
H
Inagaki
M
M
Hisamitsu
T
T
Maeda
M
M
Kochi
M
M
Sakagami
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000378:metabolism / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats
D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D005609:Free Radicals; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; C070680:zilascorb