Antineoplastic activity of BCG: location of antineoplastic glycans in the cellular integument of Mycobacterium bovis, BCG vaccine, Connaught substrain.
The polysaccharidic integument surrounding growing cells of attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine, Connaught substrain, can be removed with non-specific proteases. After 5 weeks incubation at 37 degrees C in Middlebrook 7H-9 medium, the collected cells were incubated with pronase and the integument and cells separated by centrifugation in a Ficoll-Histopaque preparation. After washing and drying, the detached integument accounted for 65% w/w of the original dried cell mass. Like the original cellular material, the detached integument manifested antineoplastic activity against a murine sarcoma model in vivo. Solubilization of the otherwise insoluble integument by boiling in water or by digestion in 8 M urea significantly enhanced activity of the integument itself, by 125 and 1,100 times, respectively. Integument extracts were shown to contain mainly glucose, with smaller quantities of other sugars, consistent with the presence in BCG of high molecular weight glycans, as previously reported. It is suggested that most, if not all, of the antineoplastic activity of BCG can be accounted for by the activity associated with the high-molecular weight polysaccharidic glycans which constitute the cellular integument.
Garrido
J L
JL
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago 60607-7019, USA.
Klegerman
M E
ME
Reyes
H R
HR
Groves
M J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001500:BCG Vaccine / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009163:Mycobacterium bovis; D011135:Polysaccharides, Bacterial / Q000494:pharmacology* / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000188:drug therapy*
D000970:Antineoplastic Agents; C087507:BCG Connaught; D001500:BCG Vaccine; D011135:Polysaccharides, Bacterial