Venkateshaiah Sathisha U, Eswaraiah Mallikarjuna S, Annaiah Harish Nayaka M, Dharmesh Shylaja M
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India.
Clin Exp Metastasis. 2017 Feb;34(2):141-154. doi: 10.1007/s10585-017-9836-z. Epub 2017 Feb 3.
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.
黑色素瘤是一种令人主要担忧的恶性肿瘤，因其高死亡率和化疗失败。此前我们已表明，半乳糖凝集素-3（一种半乳糖特异性凝集素）在转移起始中起关键作用。据推测，用富含半乳糖的膳食果胶聚合物阻断半乳糖凝集素-3会抑制转移。本研究在一项关于B16F10细胞肺定植的预防性研究中，分析了来自燕子根（Decalepis hamiltonii）的一种果胶聚合物的预防效果和作用方式。通过酶谱法测定基质金属蛋白酶（MMPs）活性。通过免疫测定分析凋亡/增殖标志物和细胞因子。结果表明，与CPP的60%和GRPP的仅7%相比，SRPP对肺定植的抑制率约为88%。进一步的分子分析显示，半乳糖凝集素-3的阻断与MMPs和NFκB的下调有关。半胱天冬酶的激活支持了SRPP 的凋亡作用。CD11b细胞的存在和促炎细胞因子IL-17的释放证明了炎性细胞浸润到肺中，表明在癌细胞定植过程中存在炎症。SRPP增强了IL-12的释放，从而能够减轻炎症。我们的数据首次表明，由于半乳糖凝集素-3的阻断和免疫调节，SRPP具有有效的抗转移作用。
