*2.5. The MDR Reversal E*ff*ects of ZAs A, B, C*

To examine the MDR reversal effects of ZAs A, B, C, the cytotoxicity of a combination of these triterpenoids and chemotherapeutic drugs was evaluated in HeLaS3 and MDR KBvin cells. The IC50 of doxorubicin, paclitaxel, and vincristine in HeLa cells were 104 nM, 4.65 nM, and 41.5 nM, while in KBvin cells they were 3750 nM, 1824 nM, and 14,540 nM, indicating high multidrug resistance of the cells. When ZAs A–C were combined with the chemotherapeutic agents, the IC50 of doxorubicin, paclitaxel, and vincristine in MDR KBvin cells were significantly decreased (Table 1). Reversal folds were calculated by dividing the IC50 of the individual chemotherapeutic drug by the IC50 of the compound–drug combinations. ZA-A possessed the most significant MDR reversal effect among the tested compounds. It (20 μM) reversed drug resistance leading to an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, corresponding to reversal folds of 48, 38, and 45, respectively.


**Table 1.** The cytotoxic IC50 and reversal fold of drug resistance for ZAs A, B, C in combination with chemotherapeutic drugs in HeLaS3 and MDR KBvin cells.

<sup>1</sup> RF: Reversal fold; \* *p* < 0.05 compared with substrate drugs transport with the tested compounds.

#### **3. Materials and Methods**
