Abstract
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.
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Abbreviations
- SRPP:
-
Swallow root pectic polysaccharide
- GRPP:
-
Ginger pectic polysaccharide
- CPP:
-
Citrus pectic polysaccharide
- MMPs:
-
Matrixmetalloproteinase
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Acknowledgements
The authors wish to thank the Director, CSIR-Central Food Technological Research Institute, for his keen interest in the work and encouragement. SMD is thankful to Department of Science and Technology and Department of Biotechnology, New Delhi for the financial assistance through projects. Dr. Mahadeva, Professor of English, University of Mysore, Mysore has been acknowledged for his kind support in English correction. UVS, SEM and HMA gracefully acknowledge the Senior Fellowships provided by Indian Council of Medical Research and Council of Scientific and Industrial Research, New Delhi, India, respectively.
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Sathisha U. Venkateshaiah and Mallikarjuna S. Eswaraiah are equal first authors.
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Venkateshaiah, S.U., Eswaraiah, M.S., Annaiah, H.N.M. et al. Antimetastatic pectic polysaccharide from Decalepis hamiltonii; galectin-3 inhibition and immune-modulation. Clin Exp Metastasis 34, 141–154 (2017). https://doi.org/10.1007/s10585-017-9836-z
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DOI: https://doi.org/10.1007/s10585-017-9836-z