Modified Citrus Pectin and Cancer

 http://www.cancer.gov/cancertopics/pdq/cam/prostatesupplements/healthprofessional/page4#Section_76

Modified Citrus Pectin

Overview
General Information and History
Preclinical Studies/Animal Studies
        In vitro studies
        Animal studies
Human Studies
        Intervention studies
        Current Clinical Trials
Adverse Effects


Overview

This section contains the following key information:

• Citrus pectin is a complex polysaccharide found in the peel and pulp of citrus fruit and can be modified by treatment with high pH and temperature.
• Preclinical research suggests that modified citrus pectin (MCP) may have effects on cancer growth and metastasis through multiple potential mechanisms.
• Very limited clinical research has been done with a couple of citrus pectin-containing products. For prostate cancer patients, the results suggest some potential clinical benefits with relatively minor and infrequent adverse events.

General Information and History

Pectin is a complex polysaccharide contained in the primary cell walls of terrestrial plants. The word ‘pectin’ comes from the Greek word for congealed or curdled. Plant pectin is used in food processing as a gelling agent and also in the formulation of oral and topical medicines as a stabilizer and nonbiodegradable matrix to support controlled drug delivery.[1] Citrus pectin is found in the peel and pulp of citrus fruit and can be modified by treatment with high pH and temperature.[2] Modification results in shorter molecules that dissolve better in water and are more readily absorbed by the body than are complex, longer chain citrus pectins.[3] One of the molecular targets of MCP is galectin-3, a protein found on the surface and within mammalian cells that is involved in many cellular processes, including cell adhesion, cell activation and chemoattraction, cell growth and differentiation, the cell cycle, and apoptosis; MCP inhibits galectin-3 activity.[2]

Some research suggests that MCP may be protective against various types of cancer, including colon, lung, and prostate cancer. MCP may exert its anticancer effects by interfering with tumor cell metastasis or by inducing apoptosis.[4]

MCP was also shown to activate natural killer cells in leukemic cell cultures, suggesting it may be able to stimulate the immune system.[5]

Preclinical Studies/Animal Studies

In vitro studies

In a 2007 study, pectins were investigated for their anticancer properties. Prostate cancer cells were treated with three different pectins; citrus pectin (CP), Pectasol (PeS, a dietary supplement containing modified citrus pectin), and fractionated pectin powder (FPP). FPP induced apoptosis to a much greater degree than did CP and PeS. Further analysis revealed that treating prostate cancer cells with heated CP resulted in levels of apoptosis similar to those following treatment with FPP. This suggests that specific structural features of pectin may be responsible for its ability to induce apoptosis in prostate cancer cells.[4]

In a 2010 study, prostate cancer cells were treated with PeS or PectaSol-C, the only two MCPs previously used in human trials. The researchers postulated that, because it has a lower molecular weight, PectaSol-C may have better bioavailability than PeS. Both types of MCP were tested at a concentration of 1 mg/mL and both were effective in inhibiting cell growth and inducing apoptosis through inhibition of the MAPK/ERK signaling pathway and activation of the enzyme caspase-3.[6]

In another study, the role of galectin-3, a multifunctional endogenous lectin, in cisplatin -treated prostate cancer cells was examined. Prostate cancer cells that expressed galectin-3 were found to be resistant to the apoptotic effects of cisplatin. However, cells that did not express galectin-3 (via silencing RNA knockdown of galectin-3 expression or treatment with MCP) were susceptible to cisplatin-induced apoptosis. These findings suggest that galectin-3 expression may play a role in prostate cancer cell chemoresistance and that the efficacy of cisplatin treatment in prostate cancer may be improved by inhibiting galectin-3.[7]

Animal studies

Only a few studies have been reported on the effects of MCP in animals bearing implanted cancers and only one involving prostate cancer.[8,9] The prostate cancer study examined the effects of MCP on the metastasis of prostate cancer cells injected into rats. In the study, rats were given 0.0%, 0.01%, 0.1%, or 1.0% MCP (wt/vol) in their drinking water beginning 4 days after cancer cell injection. The analysis revealed that treatment with 0.1% and 1.0% MCP resulted in statistically significant reductions in lung metastases but did not affect primary tumor growth.[9]

Human Studies

Intervention studies

In a 2007 pilot study, patients with advanced solid tumors (various types of cancers were represented, including prostate cancer) received MCP (5 g MCP powder dissolved in water) 3 times a day for at least 8 weeks. Following treatment, improvements were reported in some measures of quality of life, including physical functioning, global health status, fatigue, pain, and insomnia. In addition, 22.5% of participants had stable disease after 8 weeks of MCP treatment, and 12.3% of participants had disease stabilization lasting more than 24 weeks.[3]

The effect of MCP on prostate-specific antigen (PSA) doubling time (PSADT) was investigated in a 2003 study. Prostate cancer patients with rising PSA levels received six PeS capsules 3 times a day (totaling 14.4 g of MCP powder daily) for 12 months. Following treatment, 7 of 10 patients had a statistically significant (P ≤ .05) increase in PSADT.[10]

Current Clinical Trials

Check NCI’s list of cancer clinical trials for CAM clinical trials on modified citrus pectin for prostate cancer that are actively enrolling patients.

General information about clinical trials is also available from the NCI Web site.

Adverse Effects

In one prospective pilot study, MCP was well tolerated by the majority of treated patients, with the most commonly reported side effects being pruritus, dyspepsia, and flatulence.[3] In another study, no serious side effects from MCP were reported, although three patients withdrew from the study due to abdominal cramps and diarrhea that improved once treatment was halted.[10]

References

1. Mohnen D: Pectin structure and biosynthesis. Curr Opin Plant Biol 11 (3): 266-77, 2008.  [PUBMED Abstract]
   
2. Glinsky VV, Raz A: Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res 344 (14): 1788-91, 2009.  [PUBMED Abstract]
   
3. Azemar M, Hildenbrand B, Haering B, et al.: Clinical benefit in patients with advanced solid tumors treated with modified citrus pectin: a prospective pilot study. Clin Med Oncol 1: 73-80, 2007. Available online . Last accessed March 20, 2014.
   
4. Jackson CL, Dreaden TM, Theobald LK, et al.: Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic function with pectin structure. Glycobiology 17 (8): 805-19, 2007.  [PUBMED Abstract]
   
5. Ramachandran C, Wilk BJ, Hotchkiss A, et al.: Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin. BMC Complement Altern Med 11: 59, 2011.  [PUBMED Abstract]
   
6. 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 9 (2): 197-203, 2010.  [PUBMED Abstract]
   
7. Wang Y, Nangia-Makker P, Balan V, et al.: Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment. Cell Death Dis 1: e101, 2010.  [PUBMED Abstract]
   
8. Hayashi A, Gillen AC, Lott JR: Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice. Altern Med Rev 5 (6): 546-52, 2000.  [PUBMED Abstract]
   
9. Pienta KJ, Naik H, Akhtar A, et al.: Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst 87 (5): 348-53, 1995.  [PUBMED Abstract]
   
10. Guess BW, Scholz MC, Strum SB, et al.: 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 (4): 301-4, 2003.  [PUBMED Abstract]
    

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