title: A myrsinol diterpene isolated from a traditional herbal medicine, LANGDU reverses multidrug resistance in breast cancer cells.
abstract: BACKGROUND
  LANGDU, a Chinese traditional herbal medicine, was the dried roots of Euphorbia prolifera Buch-Ham. The herbal medicine has been used as anti-cancer and anti-inflammatory drug in local folk medicine for several hundred years.
  
  
  OBJECTIVE
  P-glycoprotein (P-gp) is a transmembrane exporter, which can expel a variety of anti-cancer drugs. Over-expressed P-glycoprotein in cancer cells impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR). To elucidate the effect of LANGDU on MDR cancer cells, the constituents of Euphorbia prolifera Buch-Ham were analyzed. We found that a myrsinol diterpene, J196-10-1 could reverse multidrug resistance.
  
  
  METHODS
  Cytotoxicity assays were performed to measure reversal efficiency of J196-10-1. Efflux assay, ATPase assay, and real-time PCR were used to elucidate the mechanism of the chemical.
  
  
  RESULTS
  J196-10-1 could reverse the resistance to daunorubicin, vincristine, and topotecan effectively. The diterpene inhibited P-gp mediated efflux and did not alter transcription of the target gene significantly. The compound stimulated ATP hydrolysis at a low concentration and inhibited it at a high concentration.
  
  
  CONCLUSIONS
  J196-10-1 inhibits P-gp competitively and reverses P-gp induced MDR in breast cancer cells.
authors: Tianjin Union Medicine Centre, Tianjin, China.
authors: Huapeng
authors: H
authors: Wang
authors: Union Stem Cell & Gene Engineering Co., Ltd, Tianjin, China.
authors: Xiaobo
authors: X
authors: Chen
authors: College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
authors: Ting
authors: T
authors: Li
authors: College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
authors: Jing
authors: J
authors: Xu
authors: College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China. Electronic address: mayonggang@nankai.edu.cn.
authors: Yonggang
authors: Y
authors: Ma
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans
chemical_list: D004224:Diterpenes
keywords: Euphorbia prolifera Buch-Ham; MDR; Myrsinol diterpene; P-gp; Reversal agent