title: 5-Nitro-2-(3-phenylpropylamino) benzoic acid induced drug resistance to cisplatin in human erythroleukemia cell lines.
abstract: Mechanisms of cisplatin resistance in cancer cells are not fully understood. Here, we showed a critical role for the chloride channel-3 (ClC-3) in cisplatin resistance in human erythroleukemia K562 and RK562 cells. We found that a chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) could protect cells from cisplatin-induced apoptosis. NPPB treatment decreased the mRNA and the protein expression of Bax/Bcl-2, decreased the protein expressions of cytochrome C and caspase-3, and increased the mRNA expressions of cyclin D1 and ClC-3 in cells treated with cisplatin. The caspase-3 activity was decreased significantly and the rate of cell apoptosis was decreased. NPPB treatment increased CIC-3 expression, which could increase acidification of intracellular compartments, and increased sequestration of cisplatin, inducing decreased effective drug concentrations, and subsequently cell death. Collectively, our data indicate that NPPB can induce drug resistance to cisplatin by upregulating the expression of CIC-3. NPPB-induced CIC-3 expression facilitates acidification of sequestrated cisplatin, and plays an important role in preventing cisplatin-induced apoptosis in human erythroleukemia K562 and RK562 cells.
authors.affiliation: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Kang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.forename: Lian-Kun
authors.initials: LK
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009579:Nitrobenzoates / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D002945:Cisplatin