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.
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India.
Sathisha U
SU
Venkateshaiah
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India.
Mallikarjuna S
MS
Eswaraiah
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India.
Harish Nayaka M
HN
Annaiah
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India. shylaja@cftri.res.in.
Shylaja M
SM
Dharmesh
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D029062:Apocynaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002957:Citrus / Q000737:chemistry; D004032:Diet; D004354:Drug Screening Assays, Antitumor; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D020939:Zingiber officinale / Q000737:chemistry; D007155:Immunologic Factors / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000737:chemistry / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D008543:Melanins / Q000032:analysis; D008546:Melanoma, Experimental / Q000737:chemistry / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis; D018384:Oxidative Stress; D010368:Pectins / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D037502:Galectin 3; D007155:Immunologic Factors; D008543:Melanins; D009363:Neoplasm Proteins; D010368:Pectins
B16F10-mouse melanoma cells; Galectin-3; Metastasis; Swallow root pectic polysaccharide