PMID- 28058088 OWN - NLM STAT- MEDLINE DCOM- 20170313 LR - 20181113 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2016 DP - 2016 TI - Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells. PG - 7053451 LID - 10.1155/2016/7053451 [doi] LID - 7053451 AB - Reactive oxygen species (ROS) play an important role in multidrug resistance (MDR). This study aimed to investigate the effects of long-term ROS alteration on MDR in MCF-7 cells and to explore its underlying mechanism. Our study showed both long-term treatments of H(2)O(2) and glutathione (GSH) led to MDR with suppressed iROS levels in MCF-7 cells. Moreover, the MDR cells induced by 0.1 muM H(2)O(2) treatment for 20 weeks (MCF-7/ROS cells) had a higher viability and proliferative ability than the control MCF-7 cells. MCF-7/ROS cells also showed higher activity or content of intracellular antioxidants like glutathione peroxidase (GPx), GSH, superoxide dismutase (SOD), and catalase (CAT). Importantly, MCF-7/ROS cells were characterized by overexpression of MDR-related protein 1 (MRP1) and P-glycoprotein (P-gp), as well as their regulators NF-E2-related factor 2 (Nrf2), hypoxia-inducible factor 1 (HIF-1alpha), and the activation of PI3K/Akt pathway in upstream. Moreover, several typical MDR mediators, including glutathione S-transferase-pi (GST-pi) and c-Myc and Protein Kinase Calpha (PKCalpha), were also found to be upregulated in MCF-7/ROS cells. Collectively, our results suggest that ROS may be critical in the generation of MDR, which may provide new insights into understanding of mechanisms of MDR. FAU - Cen, Juan AU - Cen J AD - Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China. FAU - Zhang, Li AU - Zhang L AD - Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China. FAU - Liu, Fangfang AU - Liu F AD - Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China. FAU - Zhang, Feng AU - Zhang F AUID- ORCID: 0000-0001-7414-0450 AD - School of Pharmacy, Henan University, Kaifeng, China. FAU - Ji, Bian-Sheng AU - Ji BS AUID- ORCID: 0000-0001-9203-9663 AD - Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China. LA - eng PT - Journal Article DEP - 20161212 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Antioxidants) RN - 0 (Reactive Oxygen Species) RN - 1N3CZ14C5O (Rhodamine 123) RN - 80168379AG (Doxorubicin) RN - BBX060AN9V (Hydrogen Peroxide) RN - GAN16C9B8O (Glutathione) SB - IM MH - Antioxidants/metabolism MH - Biological Transport/drug effects MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Doxorubicin/pharmacology MH - Drug Resistance, Multiple/*drug effects MH - Drug Resistance, Neoplasm/*drug effects MH - Glutathione/pharmacology MH - Humans MH - Hydrogen Peroxide/pharmacology MH - Intracellular Space/metabolism MH - MCF-7 Cells MH - Models, Biological MH - Reactive Oxygen Species/*pharmacology MH - Rhodamine 123/pharmacology MH - Signal Transduction/drug effects MH - Time Factors MH - Up-Regulation/drug effects PMC - PMC5183793 COIS- The authors declare that there is no conflict of interests regarding the publication of this paper. EDAT- 2017/01/07 06:00 MHDA- 2017/03/14 06:00 PMCR- 2016/12/12 CRDT- 2017/01/07 06:00 PHST- 2016/08/18 00:00 [received] PHST- 2016/10/25 00:00 [revised] PHST- 2016/11/06 00:00 [accepted] PHST- 2017/01/07 06:00 [entrez] PHST- 2017/01/07 06:00 [pubmed] PHST- 2017/03/14 06:00 [medline] PHST- 2016/12/12 00:00 [pmc-release] AID - 10.1155/2016/7053451 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2016;2016:7053451. doi: 10.1155/2016/7053451. Epub 2016 Dec 12.