Thanks, P.B.
Int J Cancer 1998 Dec 9;78(6):735-9
Interleukin-2/sodium butyrate treatment cures rats bearing liver tumors
after acquired 5-fluorouracil resistance.
Cordel S, Dupas B, Douillard JY, Meflah K
INSERM U419, Institut de Biologie, Nantes, France.
We studied the effect of immunotherapy using recombinant interleukin-2 (rIL-2) in combination with a differentiating agent,
sodium butyrate (NaBut), on experimental 5-fluorouracil (5-FU)-resistant liver metastasis from colorectal cancer in rats. For
this purpose, we used direct liver injection of 5-FU resistant cells, PRObRI, in syngeneic BDIX rats to establish liver tumors.
The growth of liver metastasis was followed before and after NaBut/rIL-2 treatment by magnetic resonance imaging (MRI).
The presence of liver tumors was checked by MRI 7 days after tumor cell injection. Evaluable rats were then assigned
randomly to a control and an experimental group. The different treatments were started on day 10 and administered
intraperitoneally (i.p.). Combined NaBut/rIL-2 treatment followed by MRI on days 56 and 91 was shown both to significantly
reduce the growth of liver tumors and to prevent extrahepatic spread. In addition, NaBut/rIL-2 treatment induced a complete
regression in 50% of the rats which remained free of disease.
Int J Oncol 1998 Dec;13(6):1335-40
Tributyrin induces growth inhibitory and differentiating effects on HT-29
colon cancer cells in vitro.
Schroder C, Eckert K, Maurer HR
Institut fur Pharmazie der Freien Universitat Berlin, Germany.
Tributyrin (TB) is a prodrug of butyrate known to induce tumor cells to differentiate. We examined its effects on cell growth,
viability, cellular morphology and differentiation of HT-29 colon cancer cells in vitro, as reflected by the expression of CEA,
E-cadherin and the induction of alkaline phosphatase activity. TB, applied in a stable emulsion, inhibited tumor cell proliferation
in a reversible and dose-dependent manner (0.5-4 mM) with significant morphological changes. The IC50 value of TB was 1
mM after 6 days. For comparison, sodium butyrate, applied in equimolar concentration, inhibited cell growth with an IC50
value of 2.2 mM. TB treatment at concentrations of 0.5 mM and 2 mM resulted in an increase of the doubling times by 18%
and 160%, respectively, without any effects on cell viability. By a colorimetric immunoassay, 1.5 mM TB induced the
expression of both CEA and E-cadherin by about 260% and 100%, respectively. Furthermore, the activity of the brush border
enzyme alkaline phosphatase was enhanced in a dose-dependent manner, up to 60-fold at the maximum of 2 mM TB. Our
results show that TB is more active than butyrate in suppressing cell growth and concomitantly promoting differentiation of
HT-29 colon cancer cells. Hence it may be a promising candidate for clinical therapeutic protocols and merits further
investigation.
Cancer Res 1998 Nov 15;58(22):5168-75
c-Myb down-regulation is associated with human colon cell differentiation,
apoptosis, and decreased Bcl-2 expression.
Thompson MA, Rosenthal MA, Ellis SL, Friend AJ, Zorbas MI, Whitehead RH, Ramsay RG
Ludwig Institute for Cancer Research, P. O. Royal Melbourne Hospital, Victoria, Australia.
c-myb is expressed in human and murine colonic mucosa and elevated expression occurs in premalignant adenomatous polyps
and carcinomas. c-Myb is required for colon cell proliferation, and there is evidence of c-myb down-regulation during
differentiation. Recently, c-myb has been implicated in hematopoietic cell survival via regulation of bcl-2 gene expression.
However, c-myb expression during terminal differentiation and apoptosis in the colonic crypt has not been examined. The
experiments in this study examine the spatial and temporal expression of c-Myb protein in vivo using human colonic crypt
sections and in vitro in human colon tumor cell lines undergoing butyrate-induced differentiation and apoptosis. Electron
microscopy, together with molecular and biochemical analysis, was used to define the differentiation status of the cells. Results
demonstrate a decrease in c-Myb expression during the commitment of cells to differentiation and apoptosis. Decreased levels
of c-Myb are accompanied by a decrease in Bcl-2. These data suggest that the transcription factor c-Myb has a role in
regulating the balance between proliferation, differentiation, and apoptosis in the colonic crypt. Furthermore, elevated c-Myb
levels in colon tumor cells may lead to persistent bcl-2 expression, thus protecting tumor cells from programmed cell death. |
