Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance in HepG2/Dox cells

Tenacissimoside A (1) and 11 alpha-O-benzoyl-12 beta-O-acetyltenacigenin B (2), two derivatives of tenacigenin B (3) from the plant Marsdenia tenacissima, reversed multidrug resistance in P-glycoprotein (Pgp)-overexpressing multidrug-resistant cancer cells. The sensitivity of HepG2/Dox cells to the antitumor drugs doxorubicin, vinblastine, puromycin, and paclitexel was increased by 18, 10, 11-, and 6-fold by 20 mu g/mL (or 25 mu M) of 1 and 16-, 53-, 16-, and 326-fold by 20 mu g/mL (or 39 mu M) of 2, respectively. A preliminary mechanistic study has suggested that I might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.