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

• Published in: Clinical & experimental metastasis 2017-02, Vol.34 (2), p.141-154
• Main Authors: Venkateshaiah, Sathisha U., Eswaraiah, Mallikarjuna S., Annaiah, Harish Nayaka M., Dharmesh, Shylaja M.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apocynaceae - chemistry; Apoptosis - drug effects; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Adhesion - drug effects; Cell Division - drug effects; Citrus - chemistry; Diet; Drug Screening Assays, Antitumor; Galectin 3 - antagonists & inhibitors; Hematology; Immunologic Factors - isolation & purification; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Lung Neoplasms - chemistry; Lung Neoplasms - immunology; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Melanins - analysis; Melanoma, Experimental - chemistry; Melanoma, Experimental - immunology; Melanoma, Experimental - prevention & control; Melanoma, Experimental - secondary; Mice; Neoplasm Invasiveness; Neoplasm Proteins - analysis; Oncology; Oxidative Stress; Pectins - isolation & purification; Pectins - pharmacology; Pectins - therapeutic use; Research Paper; Surgical Oncology; Zingiber officinale - chemistry
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-017-9836-z

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.