Skip to main content
SpringerLink
Log in

Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Taxol triggers apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy. In this report, we found that Taxol treatment resulted in caspase-8-dependent apoptosis in SKOV3 human ovarian cancer cells. Moreover, Taxol-induced apoptosis was associated with caspase-3 activation. Interestingly, Taxol treatment upregulated α-2,3-sialyltransferase (ST3Gal III) expression and forced expression of ST3Gal III attenuated Taxol-induced apoptosis. Furthermore, ST3Gal III overexpression inhibited Taxol-triggered caspase-8 activation, indicating that ST3Gal III upregulation produces cellular resistance to Taxol and hence reduces the efficacy of Taxol therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244

    CAS  PubMed  Google Scholar 

  2. Haltiwanger RS, Lowe JB (2004) Role of glycosylation in development. Annu Rev Biochem 73:491–537. doi:10.1146/annurev.biochem.73.011303.074043

    Article  CAS  PubMed  Google Scholar 

  3. Pinho S, Marcos NT, Ferreira B, Carvalho AS, Oliveira MJ, Santos-Silva F, Harduin-Lepers A, Reis CA (2007) Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells. Cancer Lett 249:157–170 (Epub 2006 Sep 11)

    Article  CAS  PubMed  Google Scholar 

  4. Sperandio M, Frommhold D, Babushkina I, Ellies LG, Olson TS, Smith ML, Fritzsching B, Pauly E, Smith DF, Nobiling R, Linderkamp O, Marth JD, Ley K (2006) Alpha 2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation. Eur J Immunol 36:3207–3215. doi:10.1002/eji.200636157

    Article  CAS  PubMed  Google Scholar 

  5. Mandal C, Srinivasan GV, Chowdhury S, Chandra S, Mandal C, Schauer R, Mandal C (2008) High level of sialate-O-acetyltransferase activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL): enzyme characterization and correlation with disease status. Glycoconj J 3:3

    Google Scholar 

  6. Kean EL, Munster-Kuhnel AK, Gerardy-Schahn R (2004) CMP-sialic acid synthetase of the nucleus. Biochim Biophys Acta 1673:56–65

    CAS  PubMed  Google Scholar 

  7. Dall’Olio F, Chiricolo M (2001) Sialyltransferases in cancer. Glycoconj J 18:841–850. doi:10.1023/A:1022288022969

    Article  PubMed  Google Scholar 

  8. Chen CL, Lee WL, Tsai YC, Yuan CC, Ng HT, Wang PH (2002) Sialyltransferase family members and cervix squamous cell carcinoma. Eur J Gynaecol Oncol 23:514–518

    CAS  PubMed  Google Scholar 

  9. Hakomori S (1996) Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 56:5309–5318

    CAS  PubMed  Google Scholar 

  10. Saldova R, Royle L, Radcliffe CM, Abd Hamid UM, Evans R, Arnold JN, Banks RE, Hutson R, Harvey DJ, Antrobus R, Petrescu SM, Dwek RA, Rudd PM (2007) Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG. Glycobiology 17:1344–1356 (Epub 2007 Sep 20)

    Article  CAS  PubMed  Google Scholar 

  11. Gorelik E, Galili U, Raz A (2001) On the role of cell surface carbohydrates and their binding proteins (lectins) in tumor metastasis. Cancer Metastasis Rev 20:245–277. doi:10.1023/A:1015535427597

    Article  CAS  PubMed  Google Scholar 

  12. Hsu CC, Lin TW, Chang WW, Wu CY, Lo WH, Wang PH, Tsai YC (2005) Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids. Gynecol Oncol 96:415–422. doi:10.1016/j.ygyno.2004.10.010

    Article  CAS  PubMed  Google Scholar 

  13. Brooks SA, Carter TM, Royle L, Harvey DJ, Fry SA, Kinch C, Dwek RA, Rudd PM (2008) Altered glycosylation of proteins in cancer: what is the potential for new anti-tumour strategies. Anticancer Agents Med Chem 8:2–21. doi:10.2174/187152008783330860

    Article  CAS  PubMed  Google Scholar 

  14. Oei AL, Moreno M, Verheijen RH, Sweep FC, Thomas CM, Massuger LF, von Mensdorff-Pouilly S (2008) Induction of IgG antibodies to MUC1 and survival in patients with epithelial ovarian cancer. Int J Cancer 123:1848–1853. doi:10.1002/ijc.23725

    Article  CAS  PubMed  Google Scholar 

  15. Wang PH, Li YF, Juang CM, Lee YR, Chao HT, Ng HT, Tsai YC, Yuan CC (2002) Expression of sialyltransferase family members in cervix squamous cell carcinoma correlates with lymph node metastasis. Gynecol Oncol 86:45–52. doi:10.1006/gyno.2002.6714

    Article  CAS  PubMed  Google Scholar 

  16. Recchi MA, Hebbar M, Hornez L, Harduin-Lepers A, Peyrat JP, Delannoy P (1998) Multiplex reverse transcription polymerase chain reaction assessment of sialyltransferase expression in human breast cancer. Cancer Res 58:4066–4070

    CAS  PubMed  Google Scholar 

  17. Gretschel S, Haensch W, Schlag PM, Kemmner W (2003) Clinical relevance of sialyltransferases ST6GAL-I and ST3GAL-III in gastric cancer. Oncology 65:139–145. doi:10.1159/000072339

    Article  CAS  PubMed  Google Scholar 

  18. Crown J, O’Leary M, Ooi WS (2004) Docetaxel and paclitaxel in the treatment of breast cancer: a review of clinical experience. Oncologist 9:24–32. doi:10.1634/theoncologist.9-suppl_2-24

    Article  CAS  PubMed  Google Scholar 

  19. Fields AL, Runowicz CD (2003) Current therapies in ovarian cancer. Cancer Invest 21:148–156. doi:10.1081/CNV-120016409

    Article  PubMed  Google Scholar 

  20. Runowicz CD, Wiernik PH, Einzig AI, Goldberg GL, Horwitz SB (1993) Taxol in ovarian cancer. Cancer 71:1591–1596

    CAS  PubMed  Google Scholar 

  21. Simon GR, Bunn PA Jr (2003) Taxanes in the treatment of advanced (stage III and IV) non-small cell lung cancer (NSCLC): recent developments. Cancer Invest 21:87–104. doi:10.1081/CNV-120005919

    Article  CAS  PubMed  Google Scholar 

  22. Amadori D, Cecconetto L (2006) Gemcitabine and taxanes in metastatic breast cancer. Ann Oncol 17:v173–v176. doi:10.1093/annonc/mdj976

    Article  PubMed  Google Scholar 

  23. Rossi D, Dennetta D, Ugolini M, Alessandroni P, Catalano V, Fedeli SL, Giordani P, Casadei V, Baldelli AM, Graziano F, Catalano G (2008) Weekly paclitaxel in elderly patients (aged > or = 70 years) with advanced non-small-cell lung cancer: an alternative choice? Results of a phase II study. Clin Lung Cancer 9:280–284. doi:10.3816/CLC.2008.n.043

    Article  CAS  PubMed  Google Scholar 

  24. Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265. doi:10.1038/nrc1317

    Article  CAS  PubMed  Google Scholar 

  25. Liao PC, Lieu CH (2005) Cell cycle specific induction of apoptosis and necrosis by paclitaxel in the leukemic U937 cells. Life Sci 76:1623–1639 (Epub 2005 Jan 20)

    Article  CAS  PubMed  Google Scholar 

  26. Huisman C, Ferreira CG, Broker LE, Rodriguez JA, Smit EF, Postmus PE, Kruyt FA, Giaccone G (2002) Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line NCI-H460. Clin Cancer Res 8:596–606

    CAS  PubMed  Google Scholar 

  27. Ofir R, Seidman R, Rabinski T, Krup M, Yavelsky V, Weinstein Y, Wolfson M (2002) Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent. Cell Death Differ 9:636–642. doi:10.1038/sj.cdd.4401012

    Article  CAS  PubMed  Google Scholar 

  28. Landen CN, Kim TJ, Lin YG, Merritt WM, Kamat AA, Han LY, Spannuth WA, Nick AM, Jennnings NB, Kinch MS, Tice D, Sood AK (2008) Tumor-selective response to antibody-mediated targeting of alphavbeta3 integrin in ovarian cancer. Neoplasia 10:1259–1267

    CAS  PubMed  Google Scholar 

  29. Cao C, Lu S, Sowa A, Kivlin R, Amaral A, Chu W, Yang H, Di W, Wan Y (2008) Priming with EGFR tyrosine kinase inhibitor and EGF sensitizes ovarian cancer cells to respond to chemotherapeutical drugs. Cancer Lett 266:249–262 (Epub 2008 Apr 8)

    Article  CAS  PubMed  Google Scholar 

  30. Engels K, Knauer SK, Loibl S, Fetz V, Harter P, Schweitzer A, Fisseler-Eckhoff A, Kommoss F, Hanker L, Nekljudova V, Hermanns I, Kleinert H, Mann W, du Bois A, Stauber RH (2008) NO signaling confers cytoprotectivity through the surviving network in ovarian carcinomas. Cancer Res 68:5159–5166. doi:10.1158/0008-5472.CAN-08-0406

    Article  CAS  PubMed  Google Scholar 

  31. Duan Z, Weinstein EJ, Ji D, Ames RY, Choy E, Mankin H, Hornicek FJ (2008) Lentiviral short hairpin RNA screen of genes associated with multidrug resistance identifies PRP-4 as a new regulator of chemoresistance in human ovarian cancer. Mol Cancer Ther 7:2377–2385 (Epub 2008 Aug 7)

    Article  CAS  PubMed  Google Scholar 

  32. Grahn A, Barkhordar GS, Larson G (2002) Cloning and sequencing of nineteen transcript isoforms of the human alpha2,3-sialyltransferase gene, ST3Gal III; its genomic organisation and expression in human tissues. Glycoconj J 19:197–210. doi:10.1023/A:1024253808424

    Article  CAS  PubMed  Google Scholar 

  33. Ahn HJ, Kim YS, Kim JU, Han SM, Shin JW, Yang HO (2004) Mechanism of taxol-induced apoptosis in human SKOV3 ovarian carcinoma cells. J Cell Biochem 91:1043–1052. doi:10.1002/jcb.20006

    Article  CAS  PubMed  Google Scholar 

  34. Day TW, Najafi F, Wu CH, Safa AR (2006) Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis. Biochem Pharmacol 71:1551–1561 (Epub 2006 Mar 31)

    Article  CAS  PubMed  Google Scholar 

  35. Motwani M, Delohery TM, Schwartz GK (1999) Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. Clin Cancer Res 5:1876–1883

    CAS  PubMed  Google Scholar 

  36. Goncalves A, Braguer D, Carles G, Andre N, Prevot C, Briand C (2000) Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer cells (HT29-D4). Biochem Pharmacol 60:1579–1584. doi:10.1016/S0006-2952(00)00481-0

    Article  CAS  PubMed  Google Scholar 

  37. Oyaizu H, Adachi Y, Taketani S, Tokunaga R, Fukuhara S, Ikehara S (1999) A crucial role of caspase 3 and caspase 8 in paclitaxel-induced apoptosis. Mol Cell Biol Res Commun 2:36–41. doi:10.1006/mcbr.1999.0146

    Article  CAS  PubMed  Google Scholar 

  38. von Haefen C, Wieder T, Essmann F, Schulze-Osthoff K, Dorken B, Daniel PT (2003) Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop. Oncogene 22:2236–2247. doi:10.1038/sj.onc.1206280

    Article  Google Scholar 

  39. Park SJ, Wu CH, Gordon JD, Zhong X, Emami A, Safa AR (2004) Taxol induces caspase-10-dependent apoptosis. J Biol Chem 279:51057–51067. doi:10.1074/jbc.M406543200

    Article  CAS  PubMed  Google Scholar 

  40. Biswas RS, Cha HJ, Hardwick JM, Srivastava RK (2001) Inhibition of drug-induced Fas ligand transcription and apoptosis by Bcl-XL. Mol Cell Biochem 225:7–20. doi:10.1023/A:1012203110027

    Article  CAS  PubMed  Google Scholar 

  41. Wieder T, Essmann F, Prokop A, Schmelz K, Schulze-Osthoff K, Beyaert R, Dorken B, Daniel PT (2001) Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. Blood 97:1378–1387. doi:10.1182/blood.V97.5.1378

    Article  CAS  PubMed  Google Scholar 

  42. Perkins CL, Fang G, Kim CN, Bhalla KN (2000) The role of Apaf-1, caspase-9, and bid proteins in etoposide- or paclitaxel-induced mitochondrial events during apoptosis. Cancer Res 60:1645–1653

    CAS  PubMed  Google Scholar 

  43. Razandi M, Pedram A, Levin ER (2000) Plasma membrane estrogen receptors signal to antiapoptosis in breast cancer. Mol Endocrinol 14:1434–1447. doi:10.1210/me.14.9.1434

    Article  CAS  PubMed  Google Scholar 

  44. Perkins C, Kim CN, Fang G, Bhalla KN (1998) Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells. Cancer Res 58:4561–4566

    CAS  PubMed  Google Scholar 

  45. Fraser M, Leung B, Jahani-Asl A, Yan X, Thompson WE, Tsang BK (2003) Chemoresistance in human ovarian cancer: the role of apoptotic regulators. Reprod Biol Endocrinol 1:66. doi:10.1186/1477-7827-1-66

    Article  PubMed  Google Scholar 

  46. Richardson A, Kaye SB (2005) Drug resistance in ovarian cancer: the emerging importance of gene transcription and spatio-temporal regulation of resistance. Drug Resist Updat 8:311–321 (Epub 2005 Oct 17)

    Article  CAS  PubMed  Google Scholar 

  47. Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P (2001) The human sialyltransferase family. Biochimie 83:727–737. doi:10.1016/S0300-9084(01)01301-3

    Article  CAS  PubMed  Google Scholar 

  48. Harduin-Lepers A, Recchi MA, Delannoy P (1995) 1994, the year of sialyltransferases. Glycobiology 5:741–758. doi:10.1093/glycob/5.8.741

    Article  CAS  PubMed  Google Scholar 

  49. Tsuji S, Datta AK, Paulson JC (1996) Systematic nomenclature for sialyltransferases. Glycobiology 6:5–7. doi:10.1093/glycob/6.7.647

    Article  Google Scholar 

  50. Kitagawa H, Paulson JC (1993) Cloning and expression of human Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase. Biochem Biophys Res Commun 194:375–382. doi:10.1006/bbrc.1993.1830

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Mary D. Kraeszig for editorial assistance. This work was supported by research grants W81XWH-07-1-0410 and RO1 CA 101743 from the Department of Defense (DOD) and the National Cancer Institute, respectively, the Indiana University Cancer Center Translational Research Acceleration Collaboration (ITRAC) initiative, and the H.H. Gregg Professorship Fund to A.R.S.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indiana University School of Medicine, 1044 West Walnut St. R4-119, Indianapolis, IN, 46202, USA

    Su Huang, Travis W. Day, Mi-Ran Choi & Ahmad R. Safa

Authors
  1. Su Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Travis W. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mi-Ran Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmad R. Safa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmad R. Safa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, S., Day, T.W., Choi, MR. et al. Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity. Mol Cell Biochem 331, 81–88 (2009). https://doi.org/10.1007/s11010-009-0147-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0147-9

Keywords

Search

Navigation