Inhibition of CUG-binding protein 1 and activation of caspases are critically involved in piperazine derivative BK10007S induced apoptosis in hepatocellular carcinoma cells
| Autor: | Dong Hoon Ryu, Hee Young Kwon, Jae Yeol Lee, Jin Han Kim, Ju-Ha Kim, Sung-Hoon Kim, Min-Ho Nam, Bum Sang Shim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Apoptosis Toxicology Pathology and Laboratory Medicine Piperazines 0302 clinical medicine Medicine and Health Sciences Enzyme assays Colorimetric assays lcsh:Science Bioassays and physiological analysis Caspase Staining MTT assay Cytotoxicity Assay Multidisciplinary TUNEL assay Cell Death Animal Behavior biology Liver Diseases Liver Neoplasms Cell Staining Hep G2 Cells Gene Expression Regulation Neoplastic Oncology Cell Processes Animal Sociality Caspases 030220 oncology & carcinogenesis Hyperexpression Techniques Research Article Carcinoma Hepatocellular Antineoplastic Agents Caspase 3 Gastroenterology and Hepatology Research and Analysis Methods Caspase 8 Carcinomas 03 medical and health sciences Gastrointestinal Tumors Survivin Gene Expression and Vector Techniques Humans Molecular Biology Techniques Molecular Biology CELF1 Protein Cell Proliferation Molecular Biology Assays and Analysis Techniques Behavior lcsh:R DAPI staining Biology and Life Sciences Cancers and Neoplasms Cell Biology Hepatocellular Carcinoma Molecular biology Enzyme Activation 030104 developmental biology Terminal deoxynucleotidyl transferase Specimen Preparation and Treatment Biochemical analysis Nuclear staining Quinazolines biology.protein lcsh:Q Zoology |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0186490 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells. Also, apoptotic bodies and terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) positive cells were observed in BK10007S treated HepG2 and SK-Hep1 cells by 4',6-diamidino-2-phenylinodole (DAPI) staining and TUNEL assay, respectively. Consistently, BK10007S increased sub G1 population in HepG2 and SK-Hep1 cells by cell cycle analysis. Furthermore, Western blotting revealed that BK10007S activated the caspase cascades (caspase 8, 9 and 3), cleaved poly (ADP-ribose) polymerase (PARP), and downregulated the expression of cyclin D1, survivin and for CUG-binding protein 1 (CUGBP1 or CELF1) in HepG2 and SK-Hep1 cells. Conversely, overexpression of CUGBP1 reduced cleavages of PARP and caspase 3, cytotoxicity and subG1 population in BK10007S treated HepG2 cells. Overall, these findings provide scientific evidences that BK10007S induces apoptosis via inhibition of CUGBP1 and activation of caspases in hepatocellular carcinomas as a potent anticancer candidate. |
| Databáze: | OpenAIRE |
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