Abstract
Hepatocyte growth factor (HGF) has opposite biological activities in regulating apoptosis, also underlying molecular mechanisms are not clearly defined. We investigated HGF ability to inhibit cell death, which was induced by Doxorubicin, a DNA damaging agent. Also Survivin and XIAP mRNA levels were compared in HGF treated and non-treated cells. Cell proliferation and death were assessed using MTT assay and dye exclusion tests. Quantitative real-time PCR was used to evaluate Survivin and XIAP expression levels after treatment with HGF. ELISA was performed to quantify HGF secretion in the selected cancer cell lines media. HGF appeared to have inhibitory effect on Doxorubicin induced cell death in all of the studied cell lines. It had minimal effect on XAIP and Survivin expression levels in MRC-5, MOLT-4 and AGS cell lines; except for XIAP expression level in AGS cell line, which was increased substantially after treatment. Surprisingly, in KG-1 cell line, XIAP and Survivin expression levels were significantly reduced after HGF treatment. Although several members of IAP gene family are reported to play role in HGF mediated cytoprotective pathway, we showed that XIAP and Survivin do not seem to be involved.
Similar content being viewed by others
References
Skibinski G, Skibinska A, James K (2001) Hepatocyte growth factor (HGF) protects c-met-expressing Burkitt’s lymphoma cell lines from apoptotic death induced by DNA damaging agents. Eur J Cancer 37:1562–1569
Zarnegar R, Michalopoulos GK (1995) The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. J Cell Biol 129:1177–1180
Soki T, Tamura Y, Sinohara H et al (2000) Role of circulating vascular endothelial growth factor and hepatocyte growth factor in patients with coronary artery disease. Heart Vessels 15:105–111
Bowers DC, Fan S, Walter KA et al (2000) Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways. Cancer Res 60:4277–4283
Yamamoto T, Tanigawa N (2001) The role of surviving as a new target of diagnosis and treatment in human cancer. Med Electron Microsc 34:207–212
Sanna MG, Correia JS, Ducrey O et al (2002) IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition. Mol Cell Biol 22(6):1754–1766
Tamm I, Trepel M, Cardo-Vila M et al (2003) Peptides targeting caspase inhibitors. J Biol Chem 278(16):14401–14405
Kennedy SM, O’Driscoll L, Purcell R et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer 88(7):1077–1083
O’Driscoll L, Linehan R, Clynes M (2003) Survivin: role in normal cells and in pathological conditions. Curr Cancer Drug Targets 3(2):131–152
Holcik M, Gibson H, Korneluk RG (2001) XIAP: apoptotic brake and promising therapeutic target. Apoptosis 6(4):253–261
Takeuchi H, Kim J, Fujimoto A et al (2005) X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/c-met pathway via Akt signaling. Clin Cancer Res 11:7621–7628
Deveraux QL, Roy N, Stennicke HR et al (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17(8):2215–2223
Arakaki N, Kajihara T, Arakaki R et al (1999) Involvement of oxidative stress in tumor cytotoxic activity of hepatocyte growth factor/scatter factor. J Biol Chem 274(19):13541–13546
Gohda E, Okauchi H, Iwao M et al (1998) Hepatocyte growth factor/scatter factor and its augmentation by phorbol esters in Meth A cells. Biochem Biophys Res Commun 245:278–283
Gao M, Fan S, Goldberg ID et al (2001) Hepatocyte growth factor/scatter factor blocks the mitochondrial pathway of apoptosis signaling in breast cancer cells. J Biol Chem 276(50):47257–47265
Eldadah BA, Faden AI (2000) Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma 17(10):811–829
Fan S, Gao M, Meng Q et al (2005) Role of NF-kB signaling in hepatocyte growth factor/scatter factor-mediated cell protection. Oncogene 24:1749–1766
Christensen JG, Burrows J, Salgia R (2005) c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett 225:1–26
Funakoshi H, Nakamura T (2003) Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta 327:1–23
Imaizumi Y, Murota H, Kanda S et al (2003) Expression of the c-met proto-oncogene and its possible involvement in liver invasion in adult T-cell leukemia. Clin Cancer Res 9:181–187
Jiang WG, Martin TA, Parr C et al (2005) Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit Rev Oncol Hematol 53:35–69
Takai K, Hara J, Matsumoto K et al (1997) Hepatocyte Growth Factor is constitutively produced by human bone marrow stromal cells and indirectly promotes hematopoiesis. Blood 89(5):1560–1565
Ratajczak MZ, Marlicz W, Ratajczak J et al (1997) Effect of hepatocyte growth factor on early human haematopoietic cell development. Brit J Haematol 99:228–236
Tacchini L, Ponti CD, Matteucci E et al (2004) Hepatocyte growth factor-activated NF-kB regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines. Carcinogenesis 25(11):2089–2100
Chen F, Castranova V, Shi X (2001) New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol 159:387–397
Tracey L, Perez-Rosado A, Artiga MJ et al (2005) Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. J Pathol 206(2):123–134
Kawakami H, Tomita M, Matsuda T et al (2005) Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax. Int J Cancer 115(6):967–974
Acknowledgements
We are grateful to Professor Cantely LG (Department of Internal Medicine and Section of Nephrology, Yale University) for kindly providing recombinant HGF. Also we thank Professor Reed JC and Steve Hourmezian from Burnham Institute, Professor H Nakshatri (Department of Biochemistry and Molecular Biology, Indiana University) for their kind offers, Dr. Amanzade A and Jalal Radfar for their skilled help in cell culture work, Dr. Mahboudi F (and all members of HIV unit, Pasteur Institute of Iran) and Dr Vaziri for their thoughtful supports.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Keyhanian, K., Edalat, R., Oghalaei, A. et al. Effect of hepatocyte growth factor (HGF) on the level of Survivin & XIAP expression in several human cancer cell lines, after treating with DNA damaging agent. Mol Cell Biochem 304, 199–205 (2007). https://doi.org/10.1007/s11010-007-9500-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-007-9500-z