title: A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c.
abstract: OBJECTIVE
  We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ-685C on pituitary adenoma cells and determine the underlying mechanisms of action.
  
  
  METHODS
  A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ-685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V-FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ-685C. The effect of SZ-685C on prolactin expression was also evaluated using RT-PCR and immunoblotting. Quantitative RT-PCR was used to detect the expression of miR-200c in SZ-685C-stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR-200c mimic to identify the mechanism underling the anti-tumor effect of SZ-685C.
  
  
  RESULTS
  SZ-685C inhibited MMQ cell growth in a dose-dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ-685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ-685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR-200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR- 200c was observed in SZ-685C-treated MMQ cells. Furthermore, the overexpression of miR-200c weakened the effect of SZ-685C-induced apoptosis of MMQ cells.
  
  
  CONCLUSIONS
  Our results suggest that SZ-685C induces MMQ cell apoptosis in a miR-200c-dependent manner. Therefore, SZ-685C might be a useful alternative treatment for pituitary adenoma.
authors: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors: C-H
authors: CH
authors: Chen
authors: W-W
authors: WW
authors: Xiao
authors: X-B
authors: XB
authors: Jiang
authors: J-W
authors: JW
authors: Wang
authors: Z-G
authors: ZG
authors: Mao
authors: N
authors: N
authors: Lei
authors: X
authors: X
authors: Fan
authors: B-B
authors: BB
authors: Song
authors: C-X
authors: CX
authors: Liao
authors: H-J
authors: HJ
authors: Wang
authors: Z-G
authors: ZG
authors: She
authors: Y-H
authors: YH
authors: Zhu
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D035683:MicroRNAs / Q000235:genetics*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051381:Rats
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; C555600:MIRN200 microRNA, rat; D035683:MicroRNAs; C569938:SZ 685C