期刊
BIOORGANIC CHEMISTRY
卷 129, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.106155
关键词
Boswellia sacra; Olibanum; Tirucallane triterpenoids; Anti -proliferative; Cell apoptosis; EGFR
资金
- National Key Research and Development Program of China [2019YFC1711000]
- Killer Products Cultivation Project of Xiqing District, Tianjin [xqssj-202016]
- Scientific Research Foundation of Tianjin University of Traditional Chinese Medicine for Recruiting Teachers [XJS202210g]
Eight new tirucallane triterpenoids and two known compounds were isolated from the gum resin of Boswellia sacra. Compound 10 exhibited remarkable inhibitory activity against HepG2 cells, inducing apoptosis and inhibiting EGFR.
Eight new tirucallane triterpenoids (1-2, 5-10) along with two known compounds (3-4) were isolated from the gum resin of Boswellia sacra. Their structures were elucidated by extensive physicochemical and spectroscopic analysis, as well as computational calculations, and single crystal X-ray diffraction. Spirosacraoic acid A (1) and B (2), possess an unusual 6/5/6/5 rearranged spirocyclic carbon skeleton. All the isolates were evaluated for their anti-proliferative activity against two tumor cell lines (HepG2 and HCT-116 cells). Compound 10 displayed remarkable inhibitory activity against HepG2 cells in a dose-dependent manner with the IC50 value of 28.01 mu M. High content analysis (HCA) showed that 10 induces apoptosis in HepG2 cells. The western blotting results revealed that 10 could up-regulate the ratio of the expression of Bax/BCL-2, and promote the caspase 3 activation and PARP cleavage. Mechanically, molecular modeling studies demonstrated that 10 could dock into EGFR active site. Meanwhile 10 significantly decreased the protein expression of p-EGFR. Furthermore, inhibition of EGFR by addition of EGFR siRNA enhanced the growth inhibitory effects of 10 on HepG2 cells, indicating that the anti-tumor effect of 10 on HepG2 cells was mediated by inhibition of EGFR.
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