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Olano-Martin, E., Gibson, G. R., and Rastell, R. A. (2002). Comparison of the in vitro bifidogenic properties of pectins and pectic-oligosaccharides. J. Appl. Microbiol. 93, 505–511. doi: 10.1046/j.1365-2672.2002.01719.x In conclusion, MCP displays many anti-metastatic properties demonstrated both in vitro and in vivo, in various malignancies. Many of them, if not all, are due to its binding to the pleiotropic galectin-3 protein which is overexpressed in cancer. Due to its well tolerance and among other plant-derived products, pectin-derived GCS-100 is being explored for the maintenance therapy of patient with B-chronic lymphocytic leukemia relapse ( O’Brien and Kay, 2011). Anti-Tumor Activity of Other Forms of Modified Pectin Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol. 2020;15:123–47. Chemoresistance is a heavy burden in the treatment of cancer, especially since a large number of patients already display metastatic disease at the time of diagnosis. The vast majority of anti-cancer drugs currently used act by inducing apoptosis via the intrinsic pathway. Numerous mechanisms underlie cancer chemoresistance ( Rebucci and Michiels, 2013), but it appears that galectin-3 which is overexpressed in numerous tumor types, suppresses cell apoptosis and hence, decreases sensitivity of cancer cells to chemotherapeutic drugs ( Glinsky and Raz, 2009). Since MCP has been shown to target galectin-3, several works were dedicated to delineate MCP-induced possible re-sensitization of cancer cells to different cytotoxic molecules. Johnson et al. (2007) showed that galectin-3 targeting via MCP or via a more specific inhibitor, lactosyl- L-leucine (LL), decreased malignant endothelial cell proliferation by themselves and sensitized these cells to the cytotoxic effect of doxorubicin. These two compounds also increases metastatic-derived MDA-MB-435 cells sensitivity to taxol both in vitro and in vivo ( Glinsky et al., 2009). GCS-100, a commercially form of pH-MCP, enhanced bortezomide and dexamethasone-induced apoptosis in multiple myeloma cells and decreased viability. The effect was accompanied by a marked decrease in galectin-3 protein level ( Chauhan et al., 2005). GCS-100 also induced calpain activation in prostate cancer cells that led to their sensitization to cisplatin treatment ( Wang et al., 2010). Combination of modified pectin with different anti-cancer agents may thus represent an efficient new strategy to overcome resistance in cancer patients. Use of Pectin as a Vehicle for Drug Delivery in Cancer Menachem A, Bodner O, Pastor J, Raz A, Kloog Y. Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors. Cell Death Discov. 2015;1:15047.
the right modified citrus pectin Size matters: the role of the right modified citrus pectin
MCP: Honokiol (9:1) combination induced a synergistic effect on antioxidant activity suggesting that the mixture is significantly more efficient than individual compounds MCP inhibited the survival of TAM in hypoxia by reducing glucose uptake via downregulation of GLUT-1 in vitro Furthermore, the M2-like macrophages in primary and metastatic tumors were detected by showing CD68 + and CD206 + cells using immunofluorescence technique. In comparison to the vehicle control group, MCP significantly reduced the number of CD68 + and CD206 + cells in tumors, indicating that MCP suppressed M2-like macrophages (Figs. 7f and 8d). In addition, MCP obviously inhibited tumor angiogenesis as indicated by reduced CD31 expression in tumor tissues (Fig. 7h). Consistent with the data in vitro, the lactate acid level in tumor tissue was also decreased by MCP (Fig. 7g). Jiang J, Eliaz I, Sliva D. Synergistic and additive effects of modified citrus pectin with two polybotanical compounds, in the suppression of invasive behavior of human breast and prostate cancer cells. Integr Cancer Ther. 2013;12:145–52. The next rate-limiting step in metastasis involves tumor cell arrest in distant organ microvasculature. Galectin-3 has been shown to mediate metastatic cell adhesion to the endothelium [ 59, 60, 61, 62, 63]. MCP was demonstrated to inhibit tumor cell adhesion to the endothelium as well as cancer cell homotypic aggregation involved in metastatic cell arrest in distant organs and the formation of intravascular metastatic deposits [ 59, 64, 65, 66, 67, 68].
Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009;344:1788–91. Nishikawa H, Suzuki H. Response by Nishikawa and Suzuki to Letter Regarding Article, “Modified citrus pectin prevents blood-brain barrier disruption in mouse subarachnoid hemorrhage by inhibiting galectin-3”. Stroke. 2019;50:e137. Matarrese P, Tinari N, Semeraro ML, Natoli C, Iacobelli S, Malorni W. Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis. FEBS Lett. 2000;473:311–5. luc metastasis tumor mouse model: 1 × 10 5 4T1-luc cells (1 × 10 5/100 μL/each mouse) were intravenously injected to each mouse by tail vein. MCP (low-dose: 350 mg/kg every day; high-dose: 700 mg/kg every day) was given orally at once a day, clodronate liposomes (100 μL/10 g) was administered intravenously every 3 days. Each treatment was performed for consecutive 21 days.
PectaSol-C Modified Citrus Pectin - 120 ecoNugenics - PectaSol-C Modified Citrus Pectin - 120
Regular citrus pectin supports digestive health, but the molecules are too large to enter the circulation -- meaning benefits are restricted to the GI tract alone. PectaSol-C® MCP solves this limitation with an advanced modification process that reduces the size and structure of the pectin. This allows PectaSol-C® to absorb into the circulation and deliver total-body benefits related to cellular health, immunity and more.* Nangia-Makker P, Hogan V, Honjo Y, Baccarini S, Tait L, Bresalier R, et al. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J Natl Cancer Inst. 2002;94:1854–62. Pectin organization and composition in plant primary cell wall depend on the growth state of the plant, on the tissues and on the plant species. Its synthesis is a complex process involving numerous enzymes that are just becoming to be identified ( Atmodjo et al., 2013). Biological Activities of Oligogalacturonides in Plants Yan J, Katz A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and -independent prostate cancer cells. Integr Cancer Ther. 2010;9:197–203. Pectin is known for its anti-tumor activities already since several decades. Because of its highly complex structure, it is not surprising that it displays so many different biological activities ( Maxwell et al., 2012). In the literature, it is not easy to make the link between structure and pectin bioactivity, notably because the origin of the pectin used in the different studies and the possible chemical modifications that create molecular fragments it has undergone are not always well described. It has to be noted that differences in size of the fragments generated, in their degree of esterification (DE), in the nature of the sugar monomers present in the polysaccharide(s) and the extraction procedure are likely to have significant influence on the properties on these different types of pectin. However, six main issues will be highlighted hereunder. Effect of Pectin as a Dietary FiberMantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14:399–416. Fang T, Liu DD, Ning HM, Dan Liu, Sun JY, Huang XJ, et al. Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3. Acta Pharmacol Sin. 2018;39:1885–93.
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