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

Tenacissimoside A (1) and 11α-O-benzoyl-12β-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 μg/mL (or 25 μM) of 1 and 16-, 53-, 16-, and 326-fold by 20 7mu;g/mL (or 39 μM) of 2, respectively. A preliminary mechanistic study has suggested that 1 might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.