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O’Brien, S., and Kay, N. E. (2011). Maintenance therapy for B-chronic lymphocytic leukemia. Clin. Adv. Hematol. Oncol. 9, 22–31. Eliaz I, Raz A. Pleiotropic effects of modified citrus pectin. Nutrients. 2019 Nov 1;11(11). DOI: 10.3390/nu11112619. PMID: 31683865. PMCID: PMC6893732. Guess, B. W., Scholz, M. C., Strum, S. B., Lam, R. Y., Johnson, H. J., and Jennrich, R. I. (2003). Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer Prostatic Dis. 6, 301–304. doi: 10.1038/sj.pcan.4500679 Caffall, K. H., and Mohnen, D. (2009). The structure, function, and biosynthesis of plant cell wall pectic polysaccharides. Carbohydr. Res. 344, 1879–1900. doi: 10.1016/j.carres.2009.05.021 The mechanical role of RG-I has been less studied but it seems that RG-I may play a role in cell wall plasticity, for example by preventing HG chains to interact with Ca 2 + ions. Transgenic plants with decreased amounts of arabinans and galactans display a stiffening of their cell wall.
PectaSol Modified Citrus Pectin Powder Super-Nutrient to PectaSol Modified Citrus Pectin Powder Super-Nutrient to
Z.Y. Zhao, et al., “The Role of Modified Citrus Pectin as an Effective Chelator of Lead in Children Hospitalized with Toxic Lead Levels,” Altern. Ther. Health Med. 14(4), 34–38 (2008). R. Di, et al., “Pectic Oligosaccharide Structure-Function Relationships: Prebiotics, Inhibitors of Escherichia coli O157:H7 Adhesion and Reduction of Shiga Toxin Cytotoxicity in HT29 Cells,” Food Chem. 227, 245–254 (2017). Also, in another small clinical study involving 13 men with prostate cancer who were resistant to surgery, radiation, and cryotherapy, treatment results showed that in 70% of the men, taking MCP for 12 months increased the time it took for the PSA numbers to double from baseline. This suggests that the tumor growth progressed significantly more slowly than it would otherwise [ 10]. The original and only proven effective form of MCP is prepared with a proprietary, non-GMO enzymatic process controlled by pH and heat, which breaks the long chain molecules of the native pectin to produce the correct molecular size and structure of <13 kilodaltons and <5% esterification.
REVIEW article
Ridley, B. L., O’Neill, M. A., and Mohnen, D. (2001). Pectins: structure, biosynthesis, and oligogalacturonide-related signaling. Phytochemistry 57, 929–967. doi: 10.1016/S0031-9422(01)00113-3 Extracellular Gal-3 acts as an adhesion surface protein, forming lattices with itself, binding glycoproteins and glycolipid membrane receptors and creating a gel-like biofilm that anchors other procancerous growth factors and inflammatory compounds within the extracellular matrix.
PectaSol-C Modified Citrus Pectin - 120 ecoNugenics - PectaSol-C Modified Citrus Pectin - 120
PectaSol is the ONLY available agent shown to halt the actions of “rogue protein” galectin-3 (Gal-3). Over 8,000 published studies, including large-scale clinical data, demonstrate how elevated Gal-3 impacts cellular health, cardiovascular health, kidney and liver function, immunity, and much more. Gal-3 is normally present in small amounts throughout the body, however, levels increase with age and other factors.* The most well-established pathogenic role of Gal-3 is in the development and migration of cancer. Gal-3 is over-expressed on the surface of cancer cells, acting as the primary adhesion molecule that allows cancers to proliferate, metastasize and evade the immune system. Not unlike most substances, there can be potential downsides to taking modified citrus pectin. MCP’s main side effects include cramping and diarrhea. These generally resolve once MCP is discontinued [ 5, 7, 10].
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Both the green banana and the pectin significantly improved intestinal permeability and also reduced diarrhea [ 13]. Increasing Sepsis Survival Elyagoby, A., Layas, N., and Wong, T. W. (2013). Colon-specific delivery of 5-fluorouracil from zinc pectinate pellets through in situ intracapsular ethylcellulose-pectin plug formation. J. Pharm. Sci. 102, 604–616. doi: 10.1002/jps.23388 Modified citrus pectin (MCP), a type of supplemental dietary fiber (a polysaccharide) made from the pulp of citrus fruits, offers a wide range of possible benefits from slowing or preventing heart disease and cancer growth to healing the gut wall and improving cognition. In May 2011, data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, a 10-year all-cause mortality investigation involving close to 8000 people, demonstrated that elevated serum Gal-3 increased all-cause mortality three-fold in the general population. 7 Another compelling large-scale study showed lower levels of Gal-3 in centenarians compared with those in their sixties and seventies who didn’t live as long. 8 Substituted galacturonans make a group of various polysaccharides whose linear chain is composed of D-Gal pA residues linked in α-1,4 (as in HG) and on which are grafted other residues. Among these GS, is rhamnogalacturonan-II (RG-II). RG-II has nothing to do with RG-I, its main chain is not composed of GalA-Rhap disaccharide but of a HG chain. Four types of chains with structurally different oligosaccharides are linked to the main chain of RG-II, they are composed of 12 types of glycosyl residues bound together by at least 22 types of glycosidic bounds. One nonasaccharide (lateral chain B) and one octasaccharide (lateral chain A) are attached in C-2 of some GalA residues from the main chain and two different disaccharides are linked in C-3 of the main chain. The localization of these lateral chains one in relation to the other is not yet determined (Figure 1). RG-II is often found in dimers thanks to a borate ion located on chain A. This dimerisation seems essential for the integrity of the plant cell wall. Despite its complexity, the RG-11 structure is well conserved in vascularized plants. Very few mutants with modified RG-II have been identified until now, which indicates the importance to conserve its structure. Other GS have been described in a short number of plants. Xylogalacturonan contains β- D-xylosyl (Xylp) linked in C3 of the main chain and is present in reproductory tissues of plants like apple, carrot and cotton. Apiogalacturonan contains monomers or dimers of β- D-apioduranosyl (Apif) attached in C-2 and C-3 of the main chain. Apiogalacturonan is found in some monocotyledons ( Ridley et al., 2001; Mohnen, 2008; Caffall and Mohnen, 2009; Harholt et al., 2010; Figure 1).
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Within the galectin family, Gal-3 has unique properties. It is a beta-galactoside-binding protein involved in a wide array of biological processes, mainly related to cell cycle, immunity and injury repair. Gal-3 is found in the nucleus, cytoplasm, mitochondrion, fibroblasts, cell surface and extracellular matrix. Circulating Gal-3 levels increase with age, injury and chronic illness. L. Calvier, et al., “The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries,” JACC Heart Fail. 3(1), 59–67 (2015). From this extensive body of published literature, only one available natural agent has emerged to demonstrate the singular ability to halt and reverse the harmful effects of Gal-3: a specific form of the nutraceutical ingredient modified citrus pectin (MCP) that’s derived from citrus peel pith and enzymatically modified to precise low molecular specifications for efficacy and bioactivity (PectaSol-C). Unmodified citrus pectin does not have the same short, systemically available polysaccharide chains as MCP … and thus remains in the gastrointestinal (GI) tract. And other “modified” pectins may simply indicate that the pectin has been altered in some way, but doesn’t contain the shorter polysaccharide chains and molecular structure required for efficacy.Sun H, Jiang H, Eliaz A, Kellum JA, Peng Z, Eliaz I. Galectin-3 in septic acute kidney injury: a translational study. Crit Care. 2021 Mar 18;25(1):109. DOI: 10.1186/s13054-021-03538-0. PMID: 33736691. PMCID: PMC7977587. F. Sanchis-Gomar, et al., “Galectin-3, Osteopontin and Successful Aging,” Clin. Chem. Lab. Med. 54(5), 873–877 (2016). Despite enormous progress in oncology therapy during the last decade, especially regarding the development of “smart drugs,” cancer still remains one of the leading causes of death. Hence, the development of new therapeutic strategies remains a high priority. Natural compounds represent an important source of new “leads” with potent chemotherapeutic or chemopreventive activity. Structure-activity relationship studies have led to the development of natural molecules or of semi-synthetic analogs with higher activity or lower toxicity. Two of the best examples currently used in cancer therapy are paclitaxel and etoposide. In this review, we will describe what is known about one particular class of complex plant polysaccharides, pectin, and its potential anti-cancer activities. Description of Pectin Natural pectin is something that we’re all familiar with, even if we don’t know what it’s called. This is the spongy pulp found in the peels of citrus fruits such as oranges, limes, lemons, and grapefruit, as well as in apples and plums. George T, Brady MF. Ethylenediaminetetraacetic Acid (EDTA). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021. PMID: 33351441.
PectaSol-C Modified Citrus Pectin, 150 g, Econugenics
Cheng, H., Zhang, Z., Leng, J., Liu, D., Hao, M., Gao, X., et al. (2013). The inhibitory effects and mechanisms of rhamnogalacturonan I pectin from potato on HT-29 colon cancer cell proliferation and cell cycle progression. Int. J. Food Sci. Nutr. 64, 36–43. doi: 10.3109/09637486.2012.694853 As the research on this form of MCP continues, it’s critical to note that, in the nutraceutical world, MCP is not a carefully defined term. Experts emphasise that other “modified” citrus pectins do not offer the same benefits as the only researched, clinically studied and substantiated MCP. On the other hand, colonocyte apoptosis activation in animals fed with pectin is also largely due to butyrate, a molecule coming from pectin fermentation by colon bacteria flora ( Avivi-Green et al., 2000a, b). Indeed, intracolonic instillation of butyrate recapitulates the effect of orally administered pectin ( Avivi-Green et al., 2000b). Butyrate is also able to induce apoptosis in colonocytes in vitro in a p53-independent manner ( Kolar et al., 2007) and by inducing mitochondrial Ca 2+ overload ( Kolar et al., 2011). In parallel, both in vitro in rat intestinal epithelial cells exposed to butyrate and in mice fed with a diet supplemented with 20% pectin, TGF-ß signaling has been demonstrated to be enhanced, leading to colonocyte growth inhibition and apoptosis. Apoptosis seems to be induced via an increased expression of Id2 (inhibitor of differentiation 2), probably via inhibition of selective isoforms of HDACs ( Cao et al., 2011). Anti-Tumor Activity of pH-Modified Pectin Takei, T., Sugihara, K., Yoshida, M., and Kawakami, K. (2013). Injectable and biodegradable sugar beet pectin/gelatin hydrogels for biomedical applications. J. Biomater. Sci. Polym. Ed. 24, 1333–1342. doi: 10.1080/09205063.2012.757727 As mentioned here above, the role of the components of the plant cell wall is first to give mechanical solidity and to form a barrier from the external environment. HGs and RGII are known to be responsible for the wall rigidification. HGs have the property to form structures which are named “egg boxes.” Two HG chains are bound one to the other through interactions including bivalent Ca 2 + ions intercalated in between them ( Liners et al., 1989). This process is important for the gelling of pectin.
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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 Platt, D., and Raz, A. (1992). Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J. Natl. Cancer Inst. 84, 438–442. doi: 10.1093/jnci/84.6.438 Watanabe, K., Reddy, B. S., Weisburger, J. H., and Kritchevsky, D. (1979). Effect of dietary alfalfa, pectin, and wheat bran on azoxymethane-or methylnitrosourea-induced colon carcinogenesis in F344 rats. J. Natl. Cancer Inst. 63, 141–145.
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