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The mainstay treatment for non-small cell lung cancer (NSCLC) is chemotherapy. However, developing multidrug resistance to chemotherapy is still the main reason for relapse and poor clinical outcomes. P-glycoprotein (P-gp) is related to multidrug resistance and inhibitors of P-gp have been reported as chemosensitizers. Therefore, the aim of this present study was to evaluate the chemosensitizing effect of pure compounds isolated from Gardenia sessiliflora in NSCLC using the A549 cell line. The P-gp function was determined by measuring the intracellular accumulation of [3H]-digoxin or [3H]-paclitaxel, substrates of P-gp. Moreover, cell viability and cell death were evaluated by MTT and apoptosis assays, respectively. The screening results of eight pure compounds revealed that compound 8 showed the most significant increase in accumulation of [3H]-digoxin and [3H]-paclitaxel. Compound 8 at 10 µM did not affect cell viability, whereas paclitaxel significantly decreased cell viability. Interestingly, the combination of compound 8 and paclitaxel significantly decreased cell viability and demonstrated a greater increase in the apoptosis population of A549 cells than a single treatment of paclitaxel. The results of this study indicated that cycloartane triterpenoids compound 8 isolated from Gardenia sessiliflora increased the anti-cancer effect of paclitaxel in A549 cells via the inhibition of P-gp-mediated drug efflux.
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