Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin.

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J Natl Cancer Inst. 1995 Mar 1;87(5):348-53.

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J Natl Cancer Inst. 1995 Mar 1;87(5):331-2.

Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin.
 
Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle TS, Lehr J, Donat TL, Tait L, Hogan V, Raz A.
 
Division of Hematology and Oncology, Wayne State University School of Medicine, Detroit, Mich.
BACKGROUND:
Prostate cancer is the most common cancer diagnosed in U.S. men and
remains incurable once it has metastasized. Many stages of the
metastatic cascade involve cellular interactions mediated by cell
surface components, such as carbohydrate-binding proteins, including
galactoside-binding lectins (galectins). Modified citrus pectin
(pH-modified), a soluble component of plant fiber derived from citrus
fruit, has been shown to interfere with cell-cell interactions mediated
by cell surface carbohydrate-binding galectin-3 molecules. PURPOSE: The
aim of this study was to determine whether modified citrus pectin, a
complex polysaccharide rich in galactosyl residues, could inhibit
spontaneous metastasis of prostate adenocarcinoma cells in the rat.

METHODS: The ability of modified citrus pectin to inhibit the adhesion
of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells
was measured by 51Cr-labeling. Modified citrus pectin inhibition of
MAT-LyLu cell anchorage-independent growth was measured by colony
formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells
and human prostate carcinoma was demonstrated by immunoblotting and
immunohistochemistry. One million MAT-LyLu cells were injected
subcutaneously into the hind limb of male Copenhagen rats on day 0.
Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus
pectin continuously in their drinking water (from day 4 until necropsy
on day 30). The number of MAT-LyLu tumor colonies in the lungs were
counted.
RESULTS: Compared with 15 or 16 control rats that had lung
metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats
in the 1.0% modified citrus-pectin group had statistically significant
(two-sided; P < .03 and P < .001, respectively) reductions in
lung metastases. The lungs of the 1.0% modified citrus pectin-treated
rats had significantly (two-sided; P < .05) fewer metastatic
colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the
control group compared with 1 colony +/- 1 in the treated group).
Modified citrus pectin had no effect on the growth of the primary
tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell
adhesion to rat endothelial cells in a time- and dose-dependent manner
as well as their colony formation in semisolid medium.
CONCLUSIONS: We
present a novel therapy in which oral intake of modified citrus pectin
acts as a potent inhibitor of spontaneous prostate carcinoma metastasis
in the Copenhagen rat. IMPLICATIONS: Further investigations are
warranted to determine the following: 1) the role of galectin-3 in
normal and cancerous prostate tissues and 2) the ability of modified
citrus pectin to inhibit human prostate metastasis in nude mice.