Annexin A5 as a New Potential Biomarker for Cisplatin-Induced Toxicity in Human Kidney Epithelial Cells

Abstract

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profi le from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identifi ed using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Overexpression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

Characterization of pig sperm hyaluronidase and improvement of the digestibility of cumulus cell mass by recombinant pSPAM1 hyaluronidase in an in vitro fertilization assay

“…HEK 293 cells were transfected transiently or stably with 10 g of plasmid construct by lipofectamine 2000 (Kim et al, 2003). The cells cultured at 37 • C and 5% CO 2 in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fatal bovine serum (FBS) in the presence of 0.5 mg/ml G418, 50 U/ml penicillin and 50 g/ml streptomycin (Kwon et al, 2013).…”

“…Pig sperm and HEK293 cells were chilled on ice for 2 h and subjected to a lysis buffer consisting of 20 mM Tris-HCl, pH 7.4, 1% Triton X-100 (TX-100), 150 mM NaCl, and 1% protease inhibitor cocktail (Sigma-Aldrich) for the extraction of proteins (Kwon et al, 2013). After centrifugation at 10,000 × g for 10 min at 4 • C, proteins retained in the supernatant were analyzed.…”

Auranofin Promotes Mitochondrial Apoptosis by Inducing Annexin A5 Expression and Translocation in Human Prostate Cancer Cells

“…Previously, it was reported that annexin A5 plays an important role in cisplatininduced mitochondria-dependent apoptosis in renal cells (Jeong et al, 2014;Kwon et al, 2013). To determine whether annexin A5 participated in auranofin-induced mitochondriadependent apoptosis, changes in annexin A5 mRNA and protein expression were measured.…”

“…Recently, data demonstrated that annexin A5 plays an important role in cisplatin-induced toxicity by mediating the mitochondrial apoptotic pathway via the induction and oligomerization of the voltage-dependent anion channel (VDAC) (Jeong et al, 2014;Kwon et al, 2013). Cisplatin is a well-known gold compound that induces mitochondria-dependent apoptosis (Xiao et al, 2003;Kim and Moon, 2012;Carvalho Rodrigues et al, 2012).…”

Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer

“…A standard treatment for late stage NSCLC is cisplatin (cis-diamminedichloroplatinum (II)) in combination with another drug, such as paclitaxel or docetaxel [2][3][4]. Because cisplatin is a non-specific anticancer drug, its therapeutic use is associated with significant off-target side effects, including nephrotoxicity [5]. Furthermore, taxanes and vincas, which are commonly used in combination with cisplatin, are neurotoxic [6].…”