Enhancement of Antiproliferative and Proapoptotic Effects of Cadmium Chloride Combined with hSmac in Hepatocellular Carcinoma Cells

Background: To study the effects of cadmium chloride (CdCl2) combined with hSmac on the proliferation and apoptosis of hepatocellular carcinoma cells, i.e. SMMC-7721. Methods: SMMC-7721 cells were transfected with pcDNA3.1+-hSmac using a lipofectamine-mediated method, and then cell viability was detected by MTT assay after exposure to 10, 20, and 30 µmol/l CdCl2. Apoptosis was determined by both acridine orange-ethidium bromide staining and flow cytometry, and expressions of caspase-3, caspase-9, and cytochrome c by Western blot. Results: CdCl2 had cytotoxicity to SMMC-7721 cells, and it could inhibit proliferation in a dose-dependent manner and induce apoptosis; hSmac could inhibit proliferation and induce apoptosis independently in SMMC-7721 cells. Furthermore, cotreatment with CdCl2 and hSmac could enhance antiproliferative and proapoptotic effects in SMMC-7721 cells. Conclusions: hSmac could enhance the cytotoxicity of CdCl2.

[1]  D. Fang,et al.  Effects of Iron Deprivation on Multidrug Resistance of Leukemic K562 Cells , 2010, Chemotherapy.

[2]  G. Mendz,et al.  Hepatocellular carcinoma: prevalence and molecular pathogenesis of Helicobacter spp. , 2009, Future microbiology.

[3]  Y. Li,et al.  Preliminary studies on anti-tumor activity of 2',4'-dihydroxychalcone isolated from Herba Oxytropis in human gastric cancer MGC-803 cells. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[4]  A. Martino,et al.  Current management strategy of hepatocellular carcinoma. , 2009, World journal of gastroenterology.

[5]  S. Choi,et al.  Oxaliplatin Combined with Continuous Infusion of 5-Fluorouracil as First-Line Chemotherapy in Patients with Metastatic or Recurrent Gastric Adenocarcinoma , 2009, Chemotherapy.

[6]  S. Rana Metals and apoptosis: recent developments. , 2008, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[7]  Lei Sun,et al.  [Effects of over-expressed Smac gene coupling with cisplatin on proliferation and apoptosis of hepatocarcinoma cells]. , 2008, Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology.

[8]  S. Shankar,et al.  Smac/DIABLO enhances the therapeutic potential of chemotherapeutic drugs and irradiation, and sensitizes TRAIL-resistant breast cancer cells , 2008, Molecular Cancer.

[9]  Liu Xiao-mei Construction and expression of eukaryotic expression vector of full length human Smac gene , 2008 .

[10]  Gang Xin,et al.  Transfection of Smac/DIABLO sensitizes drug-resistant tumor cells to TRAIL or paclitaxel-induced apoptosis in vitro. , 2007, Pharmacological research.

[11]  S. Huerta,et al.  Smac/DIABLO and colon cancer. , 2007, Anti-cancer agents in medicinal chemistry.

[12]  S. Bao,et al.  Relationship between expression of Smac and Survivin and apoptosis of primary hepatocellular carcinoma. , 2006, Hepatobiliary & pancreatic diseases international : HBPD INT.

[13]  Cristina Muñoz-Pinedo,et al.  Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Seon-Hee Oh,et al.  A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. , 2006, Toxicology and applied pharmacology.

[15]  Baohong Chen,et al.  Relative timing of redistribution of cytochrome c and Smac/DIABLO from mitochondria during apoptosis assessed by double immunocytochemistry on mammalian cells. , 2006, Experimental cell research.

[16]  L. Ying Inhibition effect of cadmium chloride on human hepatocellular carcinoma cells SMMC-7721 , 2006 .

[17]  E. Henson,et al.  MEKK1-induced apoptosis is mediated by Smac/Diablo release from the mitochondria. , 2005, Biochemical and biophysical research communications.

[18]  E. Cemeli,et al.  Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line. , 2005, Toxicology in vitro : an international journal published in association with BIBRA.

[19]  T. Motyl,et al.  Kinetics of Smac/DIABLO release from mitochondria during apoptosis of MCF‐7 breast cancer cells , 2004, Cell biology international.

[20]  O. Fardel,et al.  Cadmium induces caspase-independent apoptosis in liver Hep3B cells: role for calcium in signaling oxidative stress-related impairment of mitochondria and relocation of endonuclease G and apoptosis-inducing factor. , 2004, Free radical biology & medicine.

[21]  B. Dörken,et al.  Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-xL in a strictly caspase-3-dependent manner in human carcinoma cells , 2004, Oncogene.

[22]  B. Fox,et al.  Targeting and amplification of immune killing of tumor cells by pro‐Smac , 2004, International journal of cancer.

[23]  A. Jayasurya,et al.  Metallothioneins in human tumors and potential roles in carcinogenesis. , 2003, Mutation research.

[24]  Beverley Hale,et al.  Molecular and cellular mechanisms of cadmium carcinogenesis. , 2003, Toxicology.

[25]  B. Ng,et al.  Fibroblast Growth Factor 2-Mediated Translational Control of IAPs Blocks Mitochondrial Release of Smac/DIABLO and Apoptosis in Small Cell Lung Cancer Cells , 2003, Molecular and Cellular Biology.

[26]  K. Shiraki,et al.  Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma. , 2003, International Journal of Molecular Medicine.

[27]  I. McNeish,et al.  Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway. , 2003, Experimental cell research.

[28]  W. Park,et al.  Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[29]  K. Bhalla,et al.  Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. , 2002, Blood.

[30]  S Thameem Dheen,et al.  Metallothionein 2A expression is associated with cell proliferation in breast cancer. , 2002, Carcinogenesis.

[31]  A. Jayasurya,et al.  Proliferative potential in nasopharyngeal carcinoma: correlations with metallothionein expression and tissue zinc levels. , 2000, Carcinogenesis.

[32]  Xiaodong Wang,et al.  Smac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP Inhibition , 2000, Cell.

[33]  B. Diwan,et al.  Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. , 1999, Carcinogenesis.

[34]  J. Ward,et al.  Down-regulation of metallothionein expression in human and murine hepatocellular tumors: association with the tumor-necrotizing and antineoplastic effects of cadmium in mice. , 1996, The Journal of pharmacology and experimental therapeutics.

[35]  C. Mummery,et al.  Cadmium-induced inhibition of proliferation and differentiation of embryonal carcinoma cells and mechanistic aspects of protection by zinc. , 1993, Teratology.

[36]  J. Ward,et al.  Anticarcinogenic effects of cadmium in B6C3F1 mouse liver and lung. , 1991, Toxicology and applied pharmacology.