Granuloma-Forming Activity and Antitumor Activity of Newly Isolated Mycoloyl Glycolipid from Rhodococcus terrae 70012 (Rt. GM-2)

A newly isolated mycoloyl glycolipid (Rt. GM-2) from Rhodococcus terrae 70012 was identified and the granulomagenic and antitumor activities were studied as compared with trehalose-6, 6'-dimycolate (cord factor) also from R. terrae (Rt. TDM). The alkaline hydrolysis products of Rt. GM-2 contained trehalose, methyl-α-mycolate and a less-polar ester than the usual methyl-α-mycolate, possibly β-keto mycolate (1:1:1, by mol. ratios). On the other hand, analysis of alditol acetate obtained after the mild permethylation, NaBH4 reduction, and acetylation showed the occurrence of 2, 3, 4-tri-O-methyl-6-O-acetylglucitol. Therefore, the original glycolipid (Rt. GM-2) was identified tentatively as 6-O-α-mycoloyl 6'-O-β-ketomycoloyl trehalose. Intravenous injection of Rt. GM-2 in the form of water-in-oil-in-water emulsion caused prominent granulomas in lungs and spleen of ICR and BALB/c mice. The granulomagenic effects were as strong as those caused by Rt. TDM. The lung and spleen weights reached peaks one week after an injection of Rt. GM-2 in mice and then gradually decreased. Multiple intravenous injections of Rt. GM-2 and Rt. TDM showed antitumor activity against subcutaneously implanted Sarcoma-180, and caused prominent granulomatous changes and growthsuppression of mice.