Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2010

Open Access 01-12-2010 | Research

The roles of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells

Authors: Chunxiao Ji, Fenglian Ren, Heng Ma, Ming Xu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2010

Login to get access

Abstract

Objectives

To explore the function of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells, and discuss the signal transduetion mechanism of HepG2 cells in the apoptosis process induced by DADS by using the inhibitors of p38MAPK (SB203580) and caspase-3 (Z-DEVD-FMK).

Methods

After the human HepG2 cells had been treated with the DADS and inhibitors for 24 h, cell viability was determined by the MTT method, apoptosis was evaluated by flow cytometry (FCM) and the expressions of p38MAPK and caspase-3 were measured by western-blot.

Results

Our results indicated that DADS activities the p38MAPK and caspase-3, but the inhibitors, SB203580 and Z-DEVD-FMK (for p38MAPKand for caspase-3, respectively), both have the effect of inhibitory activity on P38MAPK and caspase-3. Furthermore, a combination treatment with both DADS and inhibitor (SB203580 or Z-DEVD-FMK) decreases the inhibitory and apoptotic activity of HepG2 cells increased compared with DADS-treated.

Conclusions

Our data indicate that p38MAPK and caspase-3 are involved in the process of DADS-induced apoptosis in human HepG2 cells and interact with each other.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tian W, Zhang Z, Cohen DM: MAPK signaling and the kidney. Am J Physiol Renal Physiol. 2000, 279: 593-604. Tian W, Zhang Z, Cohen DM: MAPK signaling and the kidney. Am J Physiol Renal Physiol. 2000, 279: 593-604.
2.
go back to reference Widmann C, Gibson S, Jarpe MB: Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999, 79: 143-180. Widmann C, Gibson S, Jarpe MB: Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999, 79: 143-180.
3.
go back to reference Tortora G, Bianco R, Daniele G: Overoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat. 2007, 10: 81-100. 10.1016/j.drup.2007.03.003.CrossRef Tortora G, Bianco R, Daniele G: Overoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat. 2007, 10: 81-100. 10.1016/j.drup.2007.03.003.CrossRef
4.
go back to reference Mendelson KG, Contois LR, Tevosian SG, Davis RJ, Paulson KE: Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver. Proc Natl Acad Sci USA. 1996, 93: 12908-13. 10.1073/pnas.93.23.12908.CrossRef Mendelson KG, Contois LR, Tevosian SG, Davis RJ, Paulson KE: Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver. Proc Natl Acad Sci USA. 1996, 93: 12908-13. 10.1073/pnas.93.23.12908.CrossRef
5.
go back to reference Niisato N, Post M, van Driessche W, Marunaka Y: Cell swelling activates stress-activated protein kinases, p38MAP kinase and JNK, in renal epithelial A6 cells. Biochem Biophys Res Commun. 1999, 266: 547-50. 10.1006/bbrc.1999.1843.CrossRef Niisato N, Post M, van Driessche W, Marunaka Y: Cell swelling activates stress-activated protein kinases, p38MAP kinase and JNK, in renal epithelial A6 cells. Biochem Biophys Res Commun. 1999, 266: 547-50. 10.1006/bbrc.1999.1843.CrossRef
6.
go back to reference Ronit H, Liola L, Hongein Li, Junying Yuan, Reuven S: Need for caspases in apoptosis of trophic factor-deprived PC12 cells. J Neuronsci Res. 1997, 50: 69-80. 10.1002/(SICI)1097-4547(19971001)50:1<69::AID-JNR8>3.0.CO;2-J.CrossRef Ronit H, Liola L, Hongein Li, Junying Yuan, Reuven S: Need for caspases in apoptosis of trophic factor-deprived PC12 cells. J Neuronsci Res. 1997, 50: 69-80. 10.1002/(SICI)1097-4547(19971001)50:1<69::AID-JNR8>3.0.CO;2-J.CrossRef
7.
go back to reference Park EK, Kwon KB, Park KI: Role of Ca2+ in diallyl diaulfide-induced apoptotic cell death of HCT-15 cells. Exp Mol Med. 2002, 34: 250-257.CrossRef Park EK, Kwon KB, Park KI: Role of Ca2+ in diallyl diaulfide-induced apoptotic cell death of HCT-15 cells. Exp Mol Med. 2002, 34: 250-257.CrossRef
8.
go back to reference Hong YS, Ham YA, Choi JH: Effects of diallyl disulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non-small lung cancer cell lines. Exp Mol Med. 2000, 32: 127-134.CrossRef Hong YS, Ham YA, Choi JH: Effects of diallyl disulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non-small lung cancer cell lines. Exp Mol Med. 2000, 32: 127-134.CrossRef
9.
go back to reference Nakagawa H, Tsuta K, Kiuchui K: Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines. Carcinogenesis. 2001, 22: 891-897. 10.1093/carcin/22.6.891.CrossRef Nakagawa H, Tsuta K, Kiuchui K: Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines. Carcinogenesis. 2001, 22: 891-897. 10.1093/carcin/22.6.891.CrossRef
10.
go back to reference Nagathihalli SN, Kandangath RA, Om VS: Diallyl disulfide causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. J Nutritional Biochem. 2010, 21: 405-412. 10.1016/j.jnutbio.2009.01.015.CrossRef Nagathihalli SN, Kandangath RA, Om VS: Diallyl disulfide causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. J Nutritional Biochem. 2010, 21: 405-412. 10.1016/j.jnutbio.2009.01.015.CrossRef
11.
go back to reference Kwon KB, Yoo SJ, Ryu DG, Yang JY, Rho HW, Kim JS: Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol. 2002, 63: 41-47. 10.1016/S0006-2952(01)00860-7.CrossRef Kwon KB, Yoo SJ, Ryu DG, Yang JY, Rho HW, Kim JS: Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol. 2002, 63: 41-47. 10.1016/S0006-2952(01)00860-7.CrossRef
12.
go back to reference Gayathri R, Gunadharini DN, Arunkumar A: Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3). Molecular and Cellular Biochemistry. 2009, 320: 197-203. 10.1007/s11010-008-9903-5.CrossRef Gayathri R, Gunadharini DN, Arunkumar A: Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3). Molecular and Cellular Biochemistry. 2009, 320: 197-203. 10.1007/s11010-008-9903-5.CrossRef
13.
go back to reference Wen J, Zhang YW, Xu M: Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells. Biochem Pharmacol. 2004, 68: 323-331. 10.1016/j.bcp.2004.03.027.CrossRef Wen J, Zhang YW, Xu M: Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells. Biochem Pharmacol. 2004, 68: 323-331. 10.1016/j.bcp.2004.03.027.CrossRef
14.
go back to reference Lu HF, Sue CC, Yu CS: Diallyl disulfide(DADS) induced apoptosis undergo capase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol. 2004, 42: 1543-1552. 10.1016/j.fct.2003.06.001.CrossRef Lu HF, Sue CC, Yu CS: Diallyl disulfide(DADS) induced apoptosis undergo capase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol. 2004, 42: 1543-1552. 10.1016/j.fct.2003.06.001.CrossRef
15.
go back to reference Marks N, Berg MJ: Recent advances on neuronal caspases in development and neurodegeneration. Neuroehem Int. 1999, 35: 195-220. 10.1016/S0197-0186(99)00061-3.CrossRef Marks N, Berg MJ: Recent advances on neuronal caspases in development and neurodegeneration. Neuroehem Int. 1999, 35: 195-220. 10.1016/S0197-0186(99)00061-3.CrossRef
16.
go back to reference Henkels KM, Turchi JJ: Cisplatin-induced apoptosis proceeds by caspases-3 dependent and independent path ways in cisplatin resistant and sensitive human ovarian cancer cell lines. Cancer Res. 1999, 59: 3077-3083. Henkels KM, Turchi JJ: Cisplatin-induced apoptosis proceeds by caspases-3 dependent and independent path ways in cisplatin resistant and sensitive human ovarian cancer cell lines. Cancer Res. 1999, 59: 3077-3083.
17.
go back to reference Chen YC, Shen SC: Emodin induces apoptosis in human promyeloeukemic HL-60 cells accompained by activation of caspase-3 cascade but independent of reactive oxygen species production. Biochem Pharmacol. 2002, 64: l7l3-1724. Chen YC, Shen SC: Emodin induces apoptosis in human promyeloeukemic HL-60 cells accompained by activation of caspase-3 cascade but independent of reactive oxygen species production. Biochem Pharmacol. 2002, 64: l7l3-1724.
18.
go back to reference Holmanova J, Vaeulova A, Kozubik A: Polvunsaturated fattyacids sensitize human colon adenocarcinoma HT-29 cells to death receptor-mediatedapoptosis. Cancer Lett. 2005, 218: 33-41. 10.1016/j.canlet.2004.07.038.CrossRef Holmanova J, Vaeulova A, Kozubik A: Polvunsaturated fattyacids sensitize human colon adenocarcinoma HT-29 cells to death receptor-mediatedapoptosis. Cancer Lett. 2005, 218: 33-41. 10.1016/j.canlet.2004.07.038.CrossRef
19.
go back to reference Kwon KB, Yoo SJ, Ryu DG: Induction ofapoptosis by dia11yl disulfide through activation of Caspase-3 in human leukemia HL-60 cells. Biochem Pharmaeol. 2002, 63: 41-47. 10.1016/S0006-2952(01)00860-7.CrossRef Kwon KB, Yoo SJ, Ryu DG: Induction ofapoptosis by dia11yl disulfide through activation of Caspase-3 in human leukemia HL-60 cells. Biochem Pharmaeol. 2002, 63: 41-47. 10.1016/S0006-2952(01)00860-7.CrossRef
20.
go back to reference Zhu XF, Liu ZC, Xie BF: Involvement of caspase-3 activation in squamocin-induced apoptosis in leukemia cell line HL-60. Life Sci. 2002, 70: l259-1269. 10.1016/S0024-3205(01)01501-6.CrossRef Zhu XF, Liu ZC, Xie BF: Involvement of caspase-3 activation in squamocin-induced apoptosis in leukemia cell line HL-60. Life Sci. 2002, 70: l259-1269. 10.1016/S0024-3205(01)01501-6.CrossRef
21.
go back to reference Wen Jun, Wang Chun Xiao: Mitogen-activated protein kinase inhibitors induce apoptosis and enhance the diallyl disulfide-induced apoptotic effect in human CNE2 cells. Journal of Health Science. 2008, 54: 129-136. 10.1248/jhs.54.129.CrossRef Wen Jun, Wang Chun Xiao: Mitogen-activated protein kinase inhibitors induce apoptosis and enhance the diallyl disulfide-induced apoptotic effect in human CNE2 cells. Journal of Health Science. 2008, 54: 129-136. 10.1248/jhs.54.129.CrossRef
22.
go back to reference Xiao Dong, Choi Sunga: Diallyl trisulfide-induced apoptosis in human prostate cancer cells involves c-Jun N-terminal kinase and extracellular-signal regulated kinase-mediated phosphorylation ofBcl-2. Oncogene. 2004, 23: 5594-5606. 10.1038/sj.onc.1207747.CrossRef Xiao Dong, Choi Sunga: Diallyl trisulfide-induced apoptosis in human prostate cancer cells involves c-Jun N-terminal kinase and extracellular-signal regulated kinase-mediated phosphorylation ofBcl-2. Oncogene. 2004, 23: 5594-5606. 10.1038/sj.onc.1207747.CrossRef
23.
go back to reference Fan Yumei, Chen Hui: Opposing effects of ERK and P38 MAP kinases on Hela cell apoptosis induced by dipyrithione. Molecules and Cells. 2007, 23: 30-38. Fan Yumei, Chen Hui: Opposing effects of ERK and P38 MAP kinases on Hela cell apoptosis induced by dipyrithione. Molecules and Cells. 2007, 23: 30-38.
24.
go back to reference Wu June, Hong Li-Chun: Mitogen-activated protein kinase(MAPK) signalling pathways in HepG2 cells infected with a virulent strain of klebsiella pneumoniae. Cellular Microbiology. 2006, 8: 1467-1474. 10.1111/j.1462-5822.2006.00725.x.CrossRef Wu June, Hong Li-Chun: Mitogen-activated protein kinase(MAPK) signalling pathways in HepG2 cells infected with a virulent strain of klebsiella pneumoniae. Cellular Microbiology. 2006, 8: 1467-1474. 10.1111/j.1462-5822.2006.00725.x.CrossRef
Metadata
Title
The roles of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells
Authors
Chunxiao Ji
Fenglian Ren
Heng Ma
Ming Xu
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2010
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-29-50

Other articles of this Issue 1/2010

Journal of Experimental & Clinical Cancer Research 1/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine