Browse > Article

Induction of Apoptosis in FRTL-5 Thyroid Cells by Okadaic Acid  

Cho Ji-Hyoung (Department of Surgery, Keimyung University College of Medicine)
Chung Ki-Yong (Department of Surgery, Keimyung University College of Medicine)
Park Jong-Wook (Department of Immunology, Keimyung University College of Medicine)
Publication Information
Korean Journal of Head & Neck Oncology / v.18, no.2, 2002 , pp. 142-149 More about this Journal
Abstract
Objectve : Okadaic acid is a specific inhibitor of serine/threonine protein phosphatase 1 and 2A. In order to know the mechanism of apoptosis induced by okadaic acid, we treated FRTL-5 thyroid cells with okadaic acid and measured the changes of important proteins that are involved in apoptosis. Materials and Methods: We measured caspase 3 activity, $PLC-{\gamma}1$ degradation, the expression of XIAP, cIAP1, cIAP2, and cytochrome c release in okadaic acid-treated FRTL-5 thyroid cells. Results: Okadaic acid-induced caspase 3 activation and $PLC-{\gamma}1$ degradation and apoptosis were dose-dependent with a maximal effect at a concentration of 80 nmol and time-dependent with a maximal effect at 24 hours after treatment. The elevated caspase 3 activity in okadaic acid treated FRTL-5 thyroid cells are correlated with down-regulation of XIAP and cIAP1, but not cIAP2. General and potent inhibitor of caspases, z-VAD-fmk. abolished okadaic acid-induced caspase 3 activity and $PLC-{\gamma}1$ degradation. The release of cytochrome c in okadaic acid-induced FRTL-5 thyroid cells was dose-dependent with a maximal effect at a concentration of 80 nmol. Conclusions: These findings suggest that mechanism of okadaic acid-induced apoptosis is associated with cytochrome c release and increase of caspase 3 activation in FRTL-5 thyroid cells.
Keywords
Thyroid carcinoma; Okadaic acid; Apoptosis; Caspase 3;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Gupta S, Mukhtar H : Chemoprevention of Skin Cancer through Natural Agents. Skin Pharmacol Appl Skin Physiol 2001 ; 14 : 373-385   DOI   PUBMED
2 Kiguchi K, Glesne D, Chubb CH, Fujiki H, Huberman E : Differential induction of apoptosis in human breast tumor cells by okadaic acid and related inhibitors of protein phosphatases 1 and 2A. Cell Growth Differ. 1994 ; 5 : 995-1004   PUBMED
3 Kwon TK : Phorbol myristate acetate inhibits okadaic acid-induced apoptosis and downregulation of X-linked inhibitor of apoptosis in U937 cells. Biochem Biophys Res Commun. 2001 ; 287 : 135-141   DOI   PUBMED   ScienceOn
4 Kelloff GJ, Johnson JR, Crowell JA, et al : Approaches to the development and marketing approval of drugs that prevent cancer. Cancer Epidemiol Biomarkers Prev. 1995 ; 4 : 1-10   PUBMED
5 Ishida Y, Furukawa Y, Decaprio JA, Saito M, Griffin JD : Treatment of myeloid leukemic cells with the phosphatase inhibitor okadaic acid induces cell cycle arrest at either G1/S or G2/M dependingon dose. J Cell Physiol. 1992 ; 150 : 484-492   DOI   PUBMED
6 Lippman SM, Spitz MR : Lung cancer chemoprevention : an integratedapproach. J Clin Oncol. 2001 ; 19 : 74S-82S   PUBMED
7 Suganuma M, Fujiki H, Suguri H, et al : Okadaic acid : an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc Natl Acad Sci USA. 1988 ; 85 : 1768-1771   DOI   ScienceOn
8 Yang J, Liu X, Bhalla K, et al : Prevention of apoptosis by Bcl- 2 : release of cytochrome c from mitochondria blocked. Science. 1997 ; 275 : 1129-1132   DOI   PUBMED   ScienceOn
9 Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD : The release of cytochrome c from mitochondria : a primary site for Bcl-2 regulation of apoptosis. Science. 1997 ; 275 : 1132-1326   DOI   PUBMED   ScienceOn
10 Morimoto Y, Morimoto H, Okamura H, et al : Upregulation of the expressionofFas antigenand Fas ligand in a human submandibular gland ductal cell line by okadaicacid. Arch Oral Biol. 2000 ; 45 : 657-666   DOI   ScienceOn
11 Giese G, Wiegers W, Kubbies M, Scherbarth A, Traub P : Okadaic acid Co-induces vimentin expression and cell cycle arrest in MPC-11 mouse plasmacytoma cells. J Cell Physiol. 1995 ; 163 : 145-154   DOI   ScienceOn
12 Li DW, Xiang H, Mao YW, et al : Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. Exp Cell Res. 2001 ; 266 : 279-291   DOI   ScienceOn
13 Koriyama H, Kouchi Z, Umeda T, et al : Proteolytic activation of protein kinase C delta and epsilonby caspase-3 in U937 cells during chemotherapeutic agent-induced apoptosis. Cell Signal. 1999 ; 11 : 831-888   DOI   ScienceOn
14 Li P, Nijhawan D, Budihardjo I, et al : Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997 ; 91 : 479-489   DOI   ScienceOn
15 Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC : Cleavage of human inhibitor of apoptosis protein XIAP resultsinfragments with distinct specificities for caspases. EMBO J. 1999; 18 : 5242-5251   DOI   ScienceOn
16 Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC : The c-lAP-1 and c-lAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 1997 ; 16 : 6914-6925   DOI   ScienceOn
17 Deveraux QL, Stennicke HR, Salvesen GS, Reed JC : Endogenous inhibitors of caspases. J Clin Immunol. 1999 ; 19 : 388-398   DOI   ScienceOn
18 Qi XM, He H, Zhong H, Distelhorst CW : Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast cancer cells. Oncogene. 1997 ; 15 : 1207-1212   DOI   ScienceOn
19 Kiguchi K, Giometti C, Chubb CH, Fujiki H, Huberman E : Differentiation inductionin human breast tumor cells by okadaic acid and related inhibitors of protein phosphatases 1 and 2A. Biochem Biophys Res Commun. 1992 ; 189 : 1261-1267   DOI   ScienceOn
20 Fujiki H, Suganuma M : Tumor promotion by inhibitors of protein phosphatases 1 and 2A : the okadaic acid class of compounds. Adv Cancer Res. 1993 ; 61 : 143-194   DOI   ScienceOn
21 Grutter MG : Caspases : key players in programmedcell death. Curr Opin Struct Biol. 2000 ; 10 : 649-655   DOI   PUBMED   ScienceOn
22 Pal S, Choudhuri T, Chattopadhyay S, et al : Mechanisms of curcumin-induced apoptosis of Ehrlichs ascites carcinoma cells. Biochem Biophys Res Commun. 2001 ; 288 : 658-665   DOI   ScienceOn
23 Ames BN, Gold LS, Willett WC : The causes and prevention of cancer. Proc Natl Acad Sci USA. 1995 ; 92 : 5258-5265   DOI   ScienceOn
24 Decker P, Isenberg D, Muller S : Inhibition of caspase-3-mediated poly (ADP-ribose) polymerase(PARP) apoptotic cleavage by human PARP autoantibodies and effect on cells undergoing apoptosis. J Biol Chem. 2000 ; 275 : 9043-9046   DOI   ScienceOn
25 An B, Dou QP : Cleavage of retinoblastoma protein during apoptosis : an interleukin 1 beta-converting enzyme-like protease as candidate. Cancer Res. 1996 ; 56 : 438-442   PUBMED
26 Park JW, Choi YJ, Suh SI, et al : Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity. Carcinogenesis. 2001 ; 22 : 1633-1639   DOI   ScienceOn