Journal
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
Volume 19, Issue 5, Pages 423-435Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10286020.2016.1217520
Keywords
Pituitary adenomas; cassane-type derivatives; structure-activity relationship; caesalpin G; Wnt/beta-catenin
Funding
- Shenzhen Key Laboratory of Neurosurgery [ZDSYS20140509173142601]
- Basic research projects of Shenzhen Science and Technology Program [JCYJ20140414170821309, JCYJ20150306114616, 2920831101643895]
- Natural Science Foundation of Guangdong [2015A030313777]
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Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genus Caesalpinia have been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl3 extract of the seeds of C. minax in pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure-activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/-catenin pathway were involved in the CAG-induced apoptosis.
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