Sesquiterpenoids isolated from the flower of Inula japonica as potential antitumor leads for intervention of paclitaxel-resistant non-small-cell lung cancer

Three new sesquiterpene lactone dimers (1–3) were isolated from the flowers of Inula japonica together with twenty-two known sesquiterpene derivatives (4–25). Their structures were established on the basis of detailed spectroscopic analyses. All isolates were evaluated for their antiproliferative activities against paclitaxel-resistant human non-small-cell lung cancer cell line A549/PTX. The preliminary structure-activity relationship was discussed. Compound 24 exhibited the most potent effect with the IC50 value of 0.34 ± 0.10 μM, even more active than the clinically used drug paclitaxel (PTX, IC50 = 1.40 ± 0.52 μM). Compound 24 showed significant efficacy of arresting the cell cycle at the G2-M stage, inducing apoptosis through mitochondria-mediated pathway, and inhibiting cell migration and invasion. Furthermore, compound 24 could reverse multidrug resistance through suppressing the expression of ABC family proteins.