Inhibitory effect of trehalose dimycolate (TDM) and its stereoisometric derivatives, trehalose dicorynomycolates (TDCMs), with low toxicity on lung metastasis of tumour cells in mice
R. Watanabe et al., Inhibitory effect of trehalose dimycolate (TDM) and its stereoisometric derivatives, trehalose dicorynomycolates (TDCMs), with low toxicity on lung metastasis of tumour cells in mice, VACCINE, 17(11-12), 1999, pp. 1484-1492
We examined the effect of semisynthetic trehalose-6,6'-dimycolate (TDM) and
its synthetic stereoisomeric derivatives (trehalose 6,6'-dicorynomycolates
: TDCMs) prepared in oil-in-water (o/w) emulsion on inhibition of lung meta
stasis produced by highly metastatic murine tumour cells, colon 26-M3.1 car
cinoma and B16-BL6 melanoma cells, using experimental and spontaneous metas
tasis models. Intravenous (i.v.) administration of TDM (100 mu g/mouse) 1,
3 or 8 days before tumour inoculation significantly inhibited lung metastas
is of colon 26-M3.1 cells, in a dose-dependent manner. Single administratio
n of TDM I day after tumour inoculation also showed the therapeutic effect
on experimental lung metastasis of colon 26-M3.1 cells. Similarly, multiple
administrations of TDM after tumour inoculation resulted in a significant
inhibition of spontaneous lung metastasis of B16-BL6 cells (on day 35), alt
hough it showed no effect on suppression of tumour growth (on day 21). In c
omparison of toxicity in vivo among TDM and four TDCMs such as TDCM(2R,3R),
TDCM(2S,3R), TDCM(2R,3S) and TDCM(2S,3S), all of the TDCMs appeared to be
less toxic than TDM itself. Furthermore, all of the TDCMs were prophylactic
ally as well as therapeutically active for inhibition of lung metastasis of
both colon 26-M3.1 and B16-BL6 tumour cells, showing higher inhibitory act
ivity than that of TDM. In particular, TDCMs induced a marked suppression o
f the growth of B16-BL6 tumour cells in vivo. These results suggest that sy
stemic administration of TDM as well as TDCMs led to inhibition of tumour m
etastasis and TDCMs are mon potential to suppress tumour growth and inhibit
tumour metastasis than TDM. (C) 1999 Elsevier Science Ltd. All rights rese
rved.