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Synergistic Effects of PectaSol-C Modified Citrus Pectin an Inhibitor of Galectin-3 and Paclitaxel on Apoptosis of Human SKOV-3 Ovarian Cancer Cells

  • Hossein, Ghamartaj (Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran) ;
  • Keshavarz, Maryam (Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran) ;
  • Ahmadi, Samira (Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran) ;
  • Naderi, Nima (Neuroscience Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2013.12.31

Abstract

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

Keywords

References

  1. Ahn HJ, Kim YS, Kim JU, et al (2004). Mechanism of taxolinduced apoptosis in human SKOV3 ovarian carcinoma cells. J Cell Biochem, 91, 1043-52. https://doi.org/10.1002/jcb.20006
  2. Bae J, Lim MC, Choi JH, et al (2009). Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer. J Gynecol Oncol, 20, 101-6. https://doi.org/10.3802/jgo.2009.20.2.101
  3. Banerjee S, Gore M (2009). The future of targeted therapies in ovarian cancer. Oncologist, 14, 706-16. https://doi.org/10.1634/theoncologist.2009-0013
  4. Bankowski E, Sobolewski K, Romanowicz L, et al (1996). Collagen and glycosaminoglycans of Wharton's jelly and their alterations in EPH-gestosis. Eur J Obstet Gynecol Reprod Biol, 66, 109-17. https://doi.org/10.1016/0301-2115(96)02390-1
  5. Choi JH, Chun KH, Raz A, et al (2004). Inhibition of N-(4-hydroxyphenyl) retinamide-induced apoptosis in breast cancer cells by galectin-3. Cancer Biol Ther, 3, 447-52. https://doi.org/10.4161/cbt.3.5.808
  6. Chumworathayi B (2013). Personalized cancer treatment for ovarian cancer. Asian Pac J Cancer Prev, 14, 1661-4. https://doi.org/10.7314/APJCP.2013.14.3.1661
  7. Loeffler M, Daugas E, Susin SA, et al (2001). Dominant cell death induction by extramitochondrially targeted apoptosisinducing factor. FASEB J, 215, 758-67.
  8. Elola MT, Wolfenstein-Todel C, Troncoso MF, et al (2007). Galectins: matricellular glycan-binding proteins linking celladhesion, migration, and survival. Cell Mol Life Sci, 64, 1679-700. https://doi.org/10.1007/s00018-007-7044-8
  9. Glinsky VV, Kiriakova G, Glinskii OV, et al (2009). Synthetic galectin-3 inhibitor increases metastatic cancer cell sensitivity to taxol-induced apoptosis in vitro and in vivo. Neoplasia, 11, 901-9. https://doi.org/10.1593/neo.09594
  10. Goncalves A, Braguer D, Carles G, et al (2000). Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer cells (HT29-D4). Biochem Pharmacol, 60, 1579-84. https://doi.org/10.1016/S0006-2952(00)00481-0
  11. Inohara H, Raz A (1994). Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions. Glycoconj J, 11, 527-32. https://doi.org/10.1007/BF00731303
  12. Inohara H, Akahani S, Raz A (1998). Galectin-3 stimulates cell proliferation. Exp Cell Res, 245, 294-302. https://doi.org/10.1006/excr.1998.4253
  13. Iurisci I, Tinari N, Natoli C, et al (2000). Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res, 6, 1389-93.
  14. Jemal A, Siegel R, Ward E, et al (2006). Cancer statistics. CA Cancer J Clin, 56, 106-30. https://doi.org/10.3322/canjclin.56.2.106
  15. Kim HR, Lin HM, Biliran H, et al (1999). Cell cycle arrest and inhibition of anoikis by Galectin-3 in human breast epithelial cells. Cancer Res, 59, 4148-54.
  16. Kim MK, Sung CO, Do IG, et al (2011). Overexpression of Galectin-3 and its clinical significance in ovarian carcinoma. Int J Clin Oncol, 16, 352-8. https://doi.org/10.1007/s10147-011-0190-x
  17. Kiwaki K, Novak CM, Hsu DK (2007). Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing adipose tissue. Obesity, 15, 32-9. https://doi.org/10.1038/oby.2007.526
  18. Kuwabara I, Liu FT (1996). Galectin-3 promotes adhesion of human neutrophils to laminin. J Immunol, 156, 3939-44.
  19. Lee JW, Juliano R (2004). Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. Mol Cells, 17, 188-202.
  20. Lin HM, Pestell RG, Raz A, et al (2002). Galectin-3 enhances cyclin D1 promoter activity through SP1 and a cAMPresponsive element in human breast epithelial cells. Oncogene, 21, 8001-10. https://doi.org/10.1038/sj.onc.1205820
  21. Nangia-Makker P, Nakahara S, Hogan V, et al (2007). Galectin-3 in apoptosis, a novel therapeutic target. J Bioenerg Biomembr, 39, 79-84. https://doi.org/10.1007/s10863-006-9063-9
  22. Ochieng J, Leite-Browning ML, Warfield P (1998). Regulation of cellular adhesion to extracellular matrix proteins by galectin-3. Biochem Biophys Res Commun, 246, 788-91. https://doi.org/10.1006/bbrc.1998.8708
  23. O'Driscoll L, Linehan R, Liang YH, et al (2002). Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro. Anticancer Res, 22, 3117-25.
  24. Oka N, Nakahara S, Takenaka Y, Fukumori T, et al (2005). Galectin-3 inhibits tumor necrosis factor-related apoptosisinducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells. Cancer Res, 65, 7546-53. https://doi.org/10.1158/0008-5472.CAN-05-1197
  25. Perkins C, Kim CN, Fang G, et al (1998). Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells. Cancer Res, 8, 4561-6.
  26. Pienta KJ, Naik H, Akhtar A, et al (1995). Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst, 87, 348-53. https://doi.org/10.1093/jnci/87.5.348
  27. Platt D, Raz A (1992). Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Cancer Inst, 84, 438-42. https://doi.org/10.1093/jnci/84.6.438
  28. Sher I, Adham SA, Petrik J, et al (2009). Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis. Int J Cancer, 124, 553-61. https://doi.org/10.1002/ijc.23963
  29. Streetly MJ, Maharaj L, Joel S, et al (2010). GCS-100, a novel galectin-3 antagonist, modulates MCL-1, NOXA, and cell cycle to induce myeloma cell death. Blood, 115, 3939-48. https://doi.org/10.1182/blood-2009-10-251660
  30. Tehranian N, Sepehri H, Mehdipour P, et al (2012). Combination effect of PectaSol and Doxorubicin on viability, cell cycle arrest and apoptosis in DU-145 and LNCaP prostate cancer cell lines. Cell Biol Int, 36, 601-10. https://doi.org/10.1042/CBI20110309
  31. van den Brule FA, Berchuck A, Bast RC, et al (1994). Differential expression of the 67-kD laminin receptor and 31-kD human laminin-binding protein in human ovarian carcinomas. Eur J Cancer, 30, 1096-9. https://doi.org/10.1016/0959-8049(94)90464-2
  32. Wan SY, Zhang TF, Ding Y (2011). Galectin-3 enhances proliferation and angiogenes of endothelial cells differentiated from bone marrow mesenchymal stem cells. Transplant Proc, 43, 3933-8. https://doi.org/10.1016/j.transproceed.2011.10.050
  33. Wang Y, Nangia-Makker P, Balan V (2010). Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment. Cell Death Dis, 1, 101. https://doi.org/10.1038/cddis.2010.79
  34. Wani MC, Taylor HL, Wall ME, et al (1971). The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc, 93, 2325-7. https://doi.org/10.1021/ja00738a045
  35. Weigel TL, Lotze MT, Kim PK, et al (2000). Paclitaxel-induced apoptosis in nonsmall cell lung cancer cell lines is associated with increased caspase-3 activity. J Thorac Cardiovasc Surg, 119, 795-803. https://doi.org/10.1016/S0022-5223(00)70016-X
  36. Wongkham S, Junking M, Wongkham C, et al (2009). Suppression of galectin-3 expression enhances apoptosis and chemosensitivity in liver fluke-associated cholangiocarcinoma. Cancer Sci, 100, 2077-84. https://doi.org/10.1111/j.1349-7006.2009.01304.x
  37. Yan J, Katz A (2010). 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, 197-203. https://doi.org/10.1177/1534735410369672
  38. Zhao Q, Barclay M, Hilkens J, et al (2010). Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Molecular Cancer, 9, 154. https://doi.org/10.1186/1476-4598-9-154
  39. Zhu X, Ohtsubo M, Bohmer RM, et al (1996). Adhesiondependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein. J Cell Biol, 133, 391-403. https://doi.org/10.1083/jcb.133.2.391

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