Lung cancer is one of the leading causes of
cancer death in worldwide and required for novel therapeutic strategy. Our previous research demonstrated that the crude
acetone extract of Bupleurum scorzonerifolium (BS-AE) and its component
isochaihulactone induce antiproliferative and apoptotic effects on the
lung adenocarcinoma cell line. Structural analysis has identified
isochaihulactone as a
lignan, with a chiral center and two racemic forms (Z-
isochaihulactone and E-
isochaihulactone). In this study, Z-
isochaihulactone displayed significantly higher
tumor cytotoxicity than E-
isochaihulactone in A549 cells. The notch signaling pathway plays a pivotal role in determination of cell fate during development, while in
lung cancer, it might have oncogenic or
tumor-suppressive controversial functions. We showed that Z-
isochaihulactone induced morphological changes in the A549 cells, inhibited cell growth, and arrested the cell cycle at the G2/M phase. It also induced upregulation of the active form of Notch1 (notch intracellular domain, NICD), which further induced p21 and c-Myc expression in time- and dose-dependent manners. Administrations of Z-
isochaihulactone in nude mice can significantly inhibit
tumor growth due to enhancement of NICD expression confirmed by immunohistochemical analysis. Taken together, our results supported that Z-
isochaihulactone can efficiently inhibit tumorigenicity and be a potential compound for
therapy.