Potential therapeutic role of Z-isochaihulactone in lung cancer through induction of apoptosis via notch signaling
Journal
Evidence-based Complementary and Alternative Medicine
Journal Volume
2012
Pages
809204
Date Issued
2012
Author(s)
Ou J.-P.
Lin H.-Y.
Tseng I.-H.
Chen C.-J.
Hsu H.-C.
Chan D.-C.
Sophia Chen Y.-L.
Abstract
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. ? 2012 Jie-Ping Ou et al.
SDGs
Other Subjects
antineoplastic agent; isochaihulactone; Myc protein; Notch receptor; unclassified drug; animal cell; animal tissue; antineoplastic activity; apoptosis; article; cancer growth; cancer inhibition; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; cell fate; controlled study; dose response; growth inhibition; human; human cell; immunohistochemistry; lung cancer; morphology; nonhuman; priority journal; signal transduction; upregulation
Type
journal article