1
PECTIN: A POTENTIAL SOURCE FOR CANCER SUPPRESSION Keerthana S & Janani M Mentor: Jeba Samuel, Assistant Professor Dept. of Biotechnology, REC, Thandalam INTRODUCTION What is Pectin? Pectin is a branched structured heteropolysaccharide contained in the primary cell wall of the terrestrial plants. They occur as a constituent of higher-plant cell wall embedded in the cellulose fibrils. The backbone of pectins are linearly arranged 1,4-linked α-D galactosyluronic acid residues. MCP? Pectins are naturally occurring active pharmaceutical ingredient that exert multifold benefits as a drug. Their insolubility has decreased their therapeutic index as its bioavailability is very low. Modified Citrus Pectin increases the ability of pectin to biologically interact with biomolecules such as proteins and lipids. STUDY AND HYPOTHESIS “MCP inhibits cancer progression by suppressing angiogenesis and metastasis of various cancer types” Animal Models: Rats injected with human prostate cancer cells. A. Control B. C1 C. C2 D. C3 After one month, the metastasis of prostate cancer cells into lung tissue was analysed Result: Only 50% of the rats with MCP has any metastasis. 94% of the rats that drank plain water had cancer metastasize to their lungs. Human models: MCP increases the Prostate Specific Antigen(PSA) doubling time. PSADT increased in 80% of men taking MCP for 12 months. Conclusion: Presence of MCP makes it difficult for cancer cells to break off from the main tumor, aggregate and spread to other organs. CELL APOPTOSIS: Immuno-stimulation Apoptosis of cells resulting from action of MCP in • Induction of G2/m cell cycle arrest, caspase-3 activation • DNA fragmentation • MAP kinase activation • Cell proliferation • NK-cells activation MOLECULAR INTERACTION CP & MCP inactivate key transcriptional factors, cell cycle regulators and cancer metastatic factor galectin-3 Galectin-3: MCP acts as ligand, interacts and inactivates activity, which is required for cancer cell to cell adhesion/ aggregation. Transcriptional factors: MCP binds to TF like Nf-kB and AP-1 and down-regulates mRNA and protein expression of iNOS and COX2(Those involved in pathogenesis of colon cancer) Cell cycle regulator: MCP down-regulates cyclin B and cdc2 proteins which results in cell arrest in G2/M phase leading to apoptosis. PECTIN AND DETOXIFICATION Studies claim that pectin can potentially have an effect in the detoxification of hazardous chemicals and metals from human body by chelation with little side effects. It also helps in reducing metal related inflammation, reducing cholesterol levels, removing artery plaque, eliminating arthritic pain and stiffness, eliminating constipation, diarrhea and regulating blood glucose levels. It increase the healthy intestinal microflora population including Bifidobacteria and Lactobacillus in vitro MCP AND CHEMOTHERAPY • MCP targeting galectin-3 increases cancer cell sensitivity towards chemotherapeutic agents such as • cisplatin, • staurosporine, • etoposide, • doxorubicin. • MCP reverses multiple myeloma cell resistance to bortezomib and enhances apoptosis induced by dexamethasone. • American Cancer Society suggests pre-treatment or oral administration of CP or MCP before chemotherapy for cancer treatment. PECTIN AND CANCER CONCLUSION The use of natural pectic substances in the medicinal field is always beneficial because of their minimal side effects. In this review we primarily focus on pectin, CP, MCP and cancer treatment. A number of studies show that CP and MCP have potential anti-carcinogenic effects and suppress many human cancer cell activities. By analyzing the molecular mechanisms, it is now clear that CP and MCP target and inactivate galectin-3, a cancer cell survival factor, Nf-kβ, a transcription factor involved in tumorigenesis and many kinases and apoptotic markers which leads to suppression of numerous human cancers. Animal studies and human clinical studies show that CP and MCP play a major role in detoxification of metals/carcinogens from the body, which could prevent early stages of human malignancies. Oral injection of pectin, CP and MCP show a significant inhibition of tumor growth, cancer cell metastasis, invasion, angiogenesis and survival. Future studies should be focused on the isolation of bio-active pectin components which can be useful in cancer drug development. REFERENCES 1. Baldwin, J.L. and A.C. Shah, 1993. 2. Boyd, D.R. and S.J. Genuis, 2008 3. Suryakant K.Niture and Lubna Refai 4. Bresalier, R.S., P.S. Yan, J.C. Byrd, R. Lotan and A.Raz, 1997 5. Brunekreef, B. and S.T. Holgate, 2002. 6. Chauhan, D., G. Li, K. Podar, T. Hideshima and P. Neri et al., 2005. 7. Chen, C.H., M.T. Sheu, T.F. Chen, Y.C. Wang and W.CHou et al., 2006 8. Cheng, H., S. Li, Y. Fan, X. Gao and M. Hao et al.,2011 9. Cohen, A.J., M.S. Forse and S.M. Tarlo, 1993. 10. Daas, P.J., B. Boxma, A.M. Hopman, A.G. Voragen and H.A. Schols, 2001. ABBREVIATIONS CP-Citrus Pectin MCP- Modified Citrus Pectin MAPKs- Mitogen Activated Protein Kinases iNOS-Inducible Nitric Acid Synthase COX2-Cyclooxygenase2 C1,C2,C3-MCP concentrations (%weight/volume) NK- Natural Killer cells NF-κB- Nuclear factor kappa-light-chain-enhancer of activated B cells AP1-Activator Protein 1 Fig. 1. Structure of Pectin Fig.2 Metastasis of cancer Fig.3. Binding of MCP to galectin-3 Fig.5. Inactivation of Galectin-3 Fig.4. Structure of Galectin-3
