Initial characterization of an antineoplastic, polysaccharide-rich extract of Mycobacterium bovis BCG, Tice substrain.
A purified hot-water extract from Mycobacterium bovis (BCG vaccine) has been found to have significant antitumor activity against a murine sarcoma in vivo, but not in vitro, suggesting that the active compound is behaving as an immunostimulant. The material, termed PS1, has an average molecular weight of 22.4 kDa, is freely soluble in water, but has low solubility in acetone or ethanol, and is remarkably heat-stable, as is the parent BCG vaccine in terms of high-dose antitumor activity. PS1 contains at least 50% carbohydrate, consisting mainly of glucose, galactose and mannose, and about 10% lipid that may correspond to phosphatidylinositol. It shares chemical and biological properties with an arabinomannan isolated from M. tuberculosis, but it contains only trace quantities of lipoarabinomannan (LAM). Crossed immunoelectrophoresis indicated that PS1 contains the mycobacterial antigen 89, but only a single, non-migrating precipitin arc appeared on immunoelectrophoresis against a standard anti-BCG serum. PS1 appears to be non-toxic in mice up to a dose of 5 mg/kg, while as little as 70 micrograms/kg is sufficient to inhibit tumor formation significantly.
Institute for Tuberculosis Research (M/C 964), College of Pharmacy, University of Illinois at Chicago 60607-7019.
Y
Y
Lou
M E
ME
Klegerman
A
A
Muhammad
X
X
Dai
M J
MJ
Groves
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000627:therapeutic use / Q000633:toxicity; D002241:Carbohydrates / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D005260:Female; D005612:Freeze Drying; D007123:Immunoelectrophoresis, Two-Dimensional; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D009163:Mycobacterium bovis / Q000737:chemistry* / Q000145:classification; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification* / Q000627:therapeutic use / Q000633:toxicity; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000473:pathology; D012995:Solubility
D000970:Antineoplastic Agents; D002241:Carbohydrates; D011135:Polysaccharides, Bacterial