title: Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is prevalent in southern China, northern Africa, and Alaska. The prognosis for NPC patients at early stage is good, while it is poor for patients at late stages. Cancer stem cells (CSCs) have been proposed to be associated with tumor initiation, relapse and metastasis, and the poor prognosis of NPC likely results from residual CSCs after therapy. Study on the therapy targeting CSCs in NPC remains poor, though it received intensive attentions in other cancers. Here, we used NPC cell lines with high and low proportion of CSCs as models to explore the effect of nigericin, an antibiotic, on CSCs. We found that nigericin could selectively target CSCs and sensitize CSCs in NPC to the widely used clinical drug cisplatin both in vitro and in vivo. Moreover, downregulation of the polycomb group protein Bmi-1 may contribute to the inhibitory effect of nigericin on CSCs. Furthermore, by using the in vitro NPC cell models, we found that nigericin could significantly decrease the migration and invasion abilities, which are known to be associated with CSCs. Taken together, our results suggest that nigericin can selectively target CSCs in NPC, which could be a candidate CSCs targeting drug for clinical evaluation.
authors.affiliation: State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.forename: Man-Si
authors.initials: MS
authors.lastname: Wu
authors.forename: Fu-Tuo
authors.initials: FT
authors.lastname: Feng
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Hu
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Feng
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009550:Nigericin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1; D002945:Cisplatin; D009550:Nigericin
keywords: Bmi-1; Cancer stem cells; Chemotherapy; Nasopharyngeal carcinoma; Nigericin