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

• Published in: MICROBIOLOGY and IMMUNOLOGY 1990, Vol.34(1), pp.45-53
• Main Authors: Natsuhara, Yayoi, Yoshinaga, Junji, Shogaki, Takeshi, Sumi-Nishikawa, Yukie, Kurano, Satoko, Kato, Yoshiko, Kaneda, Kenji, Oka, Shiro, Yano, Ikuya
• Format: Article
• Language: English
• Subjects: 6-O- alpha -mycoloyl 6'-O- beta -ketomycoloyl trehalose; Adjuvants, Immunologic; Animals; Antineoplastic Agents - therapeutic use; Cord Factors - therapeutic use; Glycolipids - isolation & purification; Glycolipids - therapeutic use; granuloma; Granuloma - immunology; Male; Mice; Mice, Inbred BALB C; Mycolic Acids - isolation & purification; Mycolic Acids - therapeutic use; mycoloyl glycolipids; Organ Specificity; Rhodococcus; Rhodococcus - metabolism; Sarcoma - drug therapy; sarcoma 180; trehalose 6,6'-dimycolate; Tumor Cells, Cultured
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.1990.tb00990.x

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.