Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A)
prepared from brown seaweed Sargassum thunbergii.

Itoh H, Noda H, Amano H, Ito H.

Laboratory of Marine Biochemistry, Faculty of Bioresources, Mie University, Tsu,
Japan.

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an
experimental model of lung metastases induced by Lewis lung carcinoma in mice.
Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited
the development of lung metastases. Combination treatment with GIV-A and 5-FU
inhibited significantly the lung metastases. The number of peritoneal
macrophages, total cells and macrophages in the lung increased in mice treated
with GIV-A. Binding of the third component of complement (C3) cleavage products
(C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A
was enhanced, as shown by the fluorescent antibody technique. Lung metastases
were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A.
GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of
the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover,
the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood)
was increased significantly by coadministration of GIV-A. The picryl
chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was
depressed after the implantation of tumor and treatment with 5-FU. GIV-A
restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of
normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep
red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of
the spleen and thymus and the number of spleen cells, but also restored the
suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of
splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly
increased as compared with the tumor-bearing mice treated with saline.
Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the
Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor
effect of GIV-A may be correlated with the changing pattern of the Thy1.2-,
L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and
depression of the hepatic microsomal drug-metabolizing system. These findings
raise the possibility that GIV-A may have clinical value in the prevention of
cancer metastasis.

PMID: 8572581 [PubMed - indexed for MEDLINE]


Anticancer Res 1996 May-Jun;16(3A):1213-8 Related Articles, Books, LinkOut


Antitumor and antiproliferative effects of a fucan extracted from ascophyllum
nodosum against a non-small-cell bronchopulmonary carcinoma line.

Riou D, Colliec-Jouault S, Pinczon du Sel D, Bosch S, Siavoshian S, Le Bert V,
Tomasoni C, Sinquin C, Durand P, Roussakis C.

ISOMer (Institut des Substances et Organismes de la Mer), SMAB, Laboratoire de
Pharmacologie Marine, Faculte de Pharmacie, Nantes, France.

Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown
to be endowed with inhibitory effects cell growth in various experimental
models. We studied both the antiproliferative and antitumor properties of a
fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a
cell line derived from a non-small-cell human bronchopulmonary carcinoma
(NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in
vitro a reversible antiproliferative activity with a block observed in the G1
phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show
antitumor activity at subtoxic doses. These preliminary results indicate that HF
exhibits inhibitory effect both in vitro and in vivo and is very potent
antitumor agent in cancer therapy.

PMID: 8702239 [PubMed - indexed for MEDLINE]