1. Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids.
- Author
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Liang, Chengyuan, Pei, Shaomeng, Ju, Weihui, Jia, Minyi, Tian, Danni, Tang, Yonghong, and Mao, Gennian
- Subjects
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CINNAMIC acid , *ANTINEOPLASTIC agent synthesis , *APOPTOSIS , *TUMOR growth , *BCL-2 proteins , *CHROMOSOMAL translocation - Abstract
Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo . The most potent compound, 5c, arrested HepG2 cells (IC 50 = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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