| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kaewpiboon, Chutima Moon, Jeong Malilas, Waraporn Oh, Sangtaek Jeong, Hye Gwang Johnston, Randal N. Assavalapsakul, Wanchai Chung, Young-Hwa Srisuttee, Ratakorn |
| Description |
Country affiliation: Thailand Author Affiliation: Kaewpiboon C ( Department of Biology, Faculty of Science, Thaksin University, Phatthalung 93110, Thailand.); Srisuttee R ( BK21+, Department of CognoMechatronics Engineering, Pusan National University, Busan 609735, Republic of Korea.); Malilas W ( BK21+, Department of CognoMechatronics Engineering, Pusan National University, Busan 609735, Republic of Korea.); Moon J ( BK21+, Department of CognoMechatronics Engineering, Pusan National University, Busan 609735, Republic of Korea.); Oh S ( Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul 136702, Republic of Korea.); Jeong HG ( Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305764, Republic of Korea.); Johnston RN ( Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N4N1, Canada.); Assavalapsakul W ( Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.); Chung YH ( BK21+, Department of CognoMechatronics Engineering, Pusan National University, Busan 609735, Republic of Korea.) |
| Abstract |
Despite efforts to develop efficient chemotherapeutic drug strategies to treat cancer, acquired drug resistance is a commonly encountered problem. In the present study, to investigate this phenomenon, human A549 lung cancer cells resistant to the topoisomerase inhibitor etoposide (A549RTeto) were used and compared with A549 parental cells. A549RTeto cells demonstrated increased resistance to etoposideinduced apoptosis when compared with A549 parental cells. Notably, A549RTeto cells were observed to exhibit greater levels of histone deacetylase 4 (HDAC4), phosphoStat1 and Pglycoprotein [Pgp; encoded by the multidrug resistance 1 (MDR1) gene], compared with A549 cells. To address whether HDAC4 protein is involved in etoposide resistance in A549 cells, A549RTeto cells were treated with trichostatin A (TSA; an HDAC inhibitor) during etoposide treatment. The combined treatment was demonstrated to enhance etoposideinduced apoptosis and reduce expression levels of HDAC4, Pgp and phosphoStat1. In addition, the suppression of Stat1 with siRNA enhanced etoposideinduced apoptosis and reduced the expression levels of HDAC4 and Pgp, suggesting that Stat1 is essential in the regulation of resistance to etoposide, and in the upregulation of Pgp. Notably, TSA treatment reduced Pgp transcript levels but Stat1 siRNA treatment did not, suggesting that Pgp is regulated by HDAC at the transcriptional level and by Stat1 at the posttranscriptional level. These results suggest that the upregulation of Stat1 and HDAC4 determines etoposide resistance through Pgp expression in human A549 lung cancer cells. |
| ISSN |
17912997 |
| e-ISSN |
17913004 |
| Journal |
Molecular Medicine Reports |
| Issue Number |
3 |
| Volume Number |
11 |
| Language |
English |
| Publisher |
Spandidos Publications |
| Publisher Date |
2015-03-01 |
| Publisher Place |
Greece |
| Access Restriction |
Open |
| Subject Keyword |
Antineoplastic Agents, Phytogenic Pharmacology Drug Resistance, Neoplasm Genetics Etoposide Gene Expression Regulation, Neoplastic Histone Deacetylases P-glycoprotein Repressor Proteins Stat1 Transcription Factor Cell Line, Tumor Cells, Cultured Drug Effects Histone Deacetylase Inhibitors Metabolism Lung Neoplasms Phosphorylation Rna Interference Rna, Small Interfering Transcription, Genetic Research Support, Non-u.s. Gov't Discipline Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Genetics Biochemistry Molecular Biology Cancer Research Molecular Medicine Oncology |
