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

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.