A myrsinol diterpene isolated from a traditional herbal medicine, LANGDU reverses multidrug resistance in breast cancer cells

作者：Wang, Huapeng; Chen, Xiaobo; Li, Ting; Xu, Jing; Ma, Yonggang^*

来源：Journal of Ethnopharmacology, 2016, 194: 1-5.

DOI：10.1016/j.jep.2016.08.041

• MDR
• P-gp
• Myrsinol diterpene
• Euphorbia prolifera Buch-Ham
• Reversal agent

Ethnopharmacological relevance: 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.
Aim of the study: P-glycoprotein (P-gp) is a transmembrane exporter, which can expel a variety of anticancer 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.
Materials and 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.

• 出版日期2016-12-24
• 单位南开大学; 天津市人民医院