Browse > Article
http://dx.doi.org/10.5352/JLS.2007.17.8.1027

Relation of Poly(ADP-ribose) Polymerase Cleavage and Apoptosis Induced by Paclitaxel in HeLa S3 Uterine Cancer Cells  

Chang, Jeong-Hyun (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
Kim, Kwang-Youn (Department of Microbiology and Immunology, Pusan National University School of Medicine)
Ahn, Soon-Cheol (Department of Microbiology and Immunology, Pusan National University School of Medicine)
Kwon, Heun-Young (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
Publication Information
Journal of Life Science / v.17, no.8, 2007 , pp. 1027-1033 More about this Journal
Abstract
Although paclitaxel induces apoptosis of cancer cells, its exact mechanism of action is not yet known. The present study has been performed to determine whether influence of paclitaxel in HeLa $S_{3}$ uterine cancer cells. Three assays were employed in this study: cell cytotoxicity, morphological assessments of apoptotic cells (DAPI staining assay), and western blot analysis. The results indicated that paclitaxel has cytotoxic effects in HeLa $S_{3}$ cells. Especially, the $IC_{50}$ value of paclitaxel was about 1 ${\mu}M$. And morphological changes (fragmentation) of cells were observed by paclitaxel in HeLa $S_{3}$ cells. The flow cytometric analysis of paclitaxel-treated cells indicated a block of G2/M phase. The results that pacli-taxel regulates the cell cycle, especially Sub-$G_{1}$ phase. Paclitaxel induces apoptosis of HeLa $S_{3}$ cells via PARP-dependent fashion, and this apoptosis is related to disappearance of Bcl-2 proteins.
Keywords
Paclitaxel; PARP; Bcl-2;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Vikhanskaya, F., S. Vignati, P. Beccaglia, C. Ottoboni, P. Russo, M. D'Incalci and M. Broggini. 1998. Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis, Exp. Cell Res. 241, 96-101.   DOI   ScienceOn
2 Vorobiof, D. A., B. L. Rapoport, M. R. Chasen, C. Slabber, G. McMichael, R. Eek and C. Mohammed. 2004. First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. Breast 13, 219-226.   DOI   ScienceOn
3 Wieder, T., F. Essmann, A. Prokop, K. Schmelz, K. Schulze-Osthoff, R. Beyaert, B. Dorken and P. T. Daniel 2001. Activation of caspase-8 in drug-induced apoptosis of B-lyrnphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. Blood. 97, 1378-1387.   DOI   ScienceOn
4 Zanetta, G., F. Fei and C. Mangioni. 2000. Chemotherapy with paclitaxel, ifosfamide, and cisplatin for the treatment of squamous cell cervical cancer: the experience of monza, Semin. Oncol. 27, 23-27.
5 Li. P. D., I. Nijhawan, I. Budihardjo, S. M. Srinivasula, M. Ahmad, E. S. Alnemri and X. Wang. 1997. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.   DOI   ScienceOn
6 Nicholson, D. W. 1992. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6, 1028-1042.   DOI   ScienceOn
7 Fink, S. L. and B. T. Cookson. 2005. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907-1916.   DOI   ScienceOn
8 Fischer, U., R. U. Jaicke and Schulze-Osthoff, K. 2003. Many cuts to ruin: a comprehensive update of caspase substrates. Cell Death Differ. 10, 76-100.   DOI   ScienceOn
9 Gavrieli, Y, Y. Sherman and S. A. Ben-Sasson, 1992. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119(3), 493-501.   DOI   ScienceOn
10 Green, D. R. 2000. Apoptotic PathwaysPaper Wraps Stone Blunts Scissors. Cell 102, 1-4.   DOI   ScienceOn
11 Holstein, A. S. and J. H Raymond. 2001. Synergistic Interaction of Lovastatin and Paclitaxel in Human Cancer Cells. Mol. Cancer Thera. 1, 141-149.
12 Homburg, C. H, M. de Haas, A. E. von dem Borne, A. J. Verhoeven, C. P. Reutelingsperger and D. Roos. 1995. Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro. Blood. 85, 532-540.
13 Hu, Y., M. A. Benedict, L. Ding and G. Nunez. 1999. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis, EMBO J. 18, 3586-3595.   DOI   ScienceOn
14 Park, S. J., C. H. Wu and D. John. 2004. Gordon Xiaoling Zhong, Armaghan Emami and Ahmad R. Safa. Taxol Induces Caspase-10-dependent Apoptosis. J. Bio. Chem. 279, 51057-51067.   DOI   ScienceOn
15 Ofir, R., R. Seidman, T. Rabinski, M. Krup, V. Yavelsky, Y. Weinstein and M. Wolfson. 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   ScienceOn
16 Okahashi, N., M. Koide, E. Jimi, T. Suda and T. Nishihara. 1998. Caspases (interleukin-1beta-converting enzyme family proteases) are involved in the regulation of the survival of osteoclasts. Bone 23, 33-41.   DOI   ScienceOn
17 Peter, M. E. and P. H. Krammer. 2003. The CD95 (APO-1/Fas) DISC and beyond. Cell Death Differ. 10, 26-35.   DOI   ScienceOn
18 Salvesen, G. S. and V. M. Dixit. 1994. Caspase activation: the induced-proximity model. Proc. Natl. Acad. Sci. USA. 96, 10964-10967.
19 Schulze-Osthoff, K., D. Ferrari, M. Los, S. Wesselborg and M. E. Peter. 1998. Apoptosis signaling by death receptors. Eur. J. Biochem. 254, 439-459.   DOI   ScienceOn
20 Thompson, C. B. Apoptosis in the pathogenesis and treatment of disease. 1995. Science 267, 1456-1462.   DOI   ScienceOn
21 Yoo, Y. D., J. K. Park, J. Y. Choi, K. H. Lee, Y. K. Kang, C. S. Kim, S. W. Shin, Y. H. Kim and J. S. Kim. 1999. CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells. Clin. Cancer Res. 4, 3063-3068.
22 Amos, L. A. and J. Lowe. 1999. Tubulin-like protofilaments in ca-induced FtsZ sheets. Chem. Biol. 6, 65-69.   DOI   ScienceOn
23 Huisman, C., C. G. Ferreira, L. E. Broker, J. A. Rodriguez, E. F. Smit, P. E. Postmus, F. A. Kruyt and G. Giaccone. 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.
24 Howitz, S. B. 1999. Mechanism of action of taxol. Trends Phamacol. Sci. 13, 134-136.   DOI   ScienceOn
25 Jaattela, M. and M. Tschopp. 2003. Caspase-independent cell death in T lymphocytes. Nat. Immunol. 4, 416-423.   DOI   ScienceOn
26 Arends, M. J. and A. H. Wyllie. 1991. Apoptosis: mechanisms and roles in pathology. Int. Rev. Exp. Pathol. 32, 223-254.   DOI
27 Bava, S. V., T. V. Puliappadamba, A. Deepti, A. Nair, D. Karunagaran and R. J. Anto. 2005. Sensitization of Taxol-induced Apoptosis by Curcumin Involves Downregulation of Nuclear Factor-B and the Serine/Threonine Kinase Akt and Is Independent of Tubulin Polymerization. J. Bio. Chem. 280, 6301-6308.   DOI   ScienceOn
28 Crown, J. and M. O'Leary. 2000. The taxanes: an update. Lancet 355, 1176-1178.   DOI   ScienceOn
29 Benford, H. L., N. W. A. McGowan, M. H. Helfrich, M. E. Nuttall and M. J. Rogers. 2001. Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone. 28, 465-473.   DOI   ScienceOn
30 Cain, K., D. G. Brown, C. Langlais and G. M. Cohen. 1999. Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex. J. Biol. Chem. 274, 22686-22692.   DOI
31 Fadok, V. A., D. R. Voelker, P. A. Campbell, J. J. Cohen, D. L. Bratton and P. M. Henson. 1992. Exposure of ph osphatidylserine on the surface of apoptotic lymphocytes biggers specific recognition and removal by macrophages. J. Immunol. 148, 2207.
32 Kumar, S. and M. F. Lavin. 1996. The ICE family of cysteine proteases as effectors of cell death. Cell Death Differ. 3, 255-267.
33 Earnshaw, W. C. 1995. Nuclear Changes in Apoptosis. Curr. Opin. Cell Biol. 7, 337-343.   DOI   ScienceOn
34 Mullan, P. B., J. E. Quinn, P. M. Gilmore, S. McWilliams, H. Andrews, C. Gervin, N. McCabe, S. McKenna, P. White, Y. H. Song, S. Maheswaran, E. Liu, D. A. Haber, P. G. Johnston and D. P. Harkin. 2001. BRCA1 regulates the interferon gamma mediated apoptotic response. Oncogene 20, 6123-6131.   DOI   ScienceOn
35 Wood, B. L, D. F. Gibson and J. F. Tait. 1996. Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations. Blood. 88, 1873-1880.
36 Vermes, I., C. Haanen, H. Steffens-Nakken and C. Reutelingsperger 1995. Reutelingsperger ANNEXIN V J. Immunol. Meth. 184, 39.   DOI   ScienceOn
37 Jiang, X. and X. Wang, 2004. Cytochrome C-mediated apoptosis. Annu. Rev. Biochem. 73, 87-106.   DOI   ScienceOn
38 Kim, R. 2005. Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer 103, 1551-1560.   DOI   ScienceOn
39 Kohn, E. C., G Sarosy, A. Bicher, C. Link, M. Christian, S. M. Steinberg, M. Rothenberg, D. O. Adamo, P. Davis and F. P. Ognibene. 1994. Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J. Natl. Cancer Inst. 86, 18-24.   DOI   ScienceOn
40 Koopman, G., C. P. Reutelingsperger, G. A. M. Kuijten, R. M. J. Keehnen, S. T. Pals and M. H. J. van Oers, 1994. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84, 1415-1421.
41 Krauss, T., A. Huschmand Nia, V. Viereck and G. Emons. 2001. New developments in the treatment of cervical cancer. Onkologie 243, 40-45.
42 Le, N. T. and D. R. Richardson. 2002. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim. Biophys. Acta. 1603, 31-46.
43 Leung, M. F., J. A. Sokoloski and A. C. Sartorelli. 1992. Changes in microtubules, microtubule-associated proteins, and intermediate filaments during the differentiation of HL-60 leukemia cells. Cancer Res. 52, 949-954.