Antimetastatic pectic polysaccharide from Decalepis hamiltonii; galectin-3 inhibition and immune-modulation.

Melanoma is a malignant neoplasm of major
concern because of its high mortality rate and failure of
chemotherapy. Previously we have shown that galectin-3, a
galactose specific lectin, plays a pivotal role in the initiation
of metastasis. It was hypothesized that blocking galectin-3
with galactose rich dietary pectic polymer would inhibit
metastasis. The current study analyzes the preventive effect
and mode of action of a pectic polymer from Swallow Root
(Decalepis hamiltonii) in a preventative study of B16F10
cells lung colonization. Matrix metalloproteinase (MMPs)
activity was assayed by zymography. Apoptotic/proliferative
markers and cytokines were analyzed by immunoassay.
Results indicated ~88% inhibition of lung colonization
by SRPP as compared to 60% by CPP and only 7% by
GRPP. Further molecular analysis revealed that galectin-3
blockade was associated with down regulation of MMPs
and NFκB. Activation of caspases supported the apoptotic
effect of SRPP. Infiltration of inflammatory cells into
the lung was evidenced by presence of CD11b+
cells and
release of the pro-inflammatory cytokine-IL-17, indicating
inflammation during the cancer cell colonization process.
SRPP enhanced the release of IL-12 that enables the reduction
of inflammation. Our data for the first time indicate the effective anti-metastatic effect of SRPP due to both galectin-
3 blockade and immunomodulation.