In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K(3) combination.
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-microm 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
HS
Laboratoire de Pharmacologie Toxicologique et Cancérologique, Faculté de Médecine, Université Catholique de Louvain, Brussels-Woluwé, Belgium.
Jamison
J M
JM
Gilloteaux
J
J
Gwin
C A
CA
Gordon
T
T
Summers
J L
JL
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004396:Coloring Agents; D003851:Deoxyribonucleases / Q000378:metabolism*; D004357:Drug Synergism; D004793:Enzyme Reactivators / Q000494:pharmacology / Q000627:therapeutic use*; D006651:Histocytochemistry; D006801:Humans; D007854:Lead; D008297:Male; D008739:Methyl Green; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009566:Nitrates; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014812:Vitamin K / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D004396:Coloring Agents; D004793:Enzyme Reactivators; D009566:Nitrates; D014812:Vitamin K; D007854:Lead; C017461:lead nitrate; D008739:Methyl Green; D003851:Deoxyribonucleases; D001205:Ascorbic Acid