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KMID : 0043320180410060646
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Archives of Pharmacal Research
2018 Volume.41 No. 6 p.646 ~ p.654
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A new terpene coumarin microbial transformed by Mucor polymorphosporus induces apoptosis of human gastric cancer cell line MGC-803
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Li Guangzhi
Wang Junchi
Li Xiaojin
Xu Jianguo
Zhang Zhao
Si Jianyong
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Abstract
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2′-Z auraptene (1) is a synthesized monoterpene coumarin with anticancer activity against human gastric cancer cells. In order to find new potential anticancer agent, Mucor polymorphosporus was used to transform cis-auraptene. Four new terpene coumarins with notable changes in the skeletal backbone, 2′-Z auraptene A-D (2?5), were obtained and evaluated for their antiproliferative effects against human normal gastric epithelium cells and human gastric cancer cells. These new compounds showed selective cytotoxic activity against MGC-803 cells with IC50 values from 0.78?±?0.13 to 10.78?±?1.83 μM and the therapeutic index could also be significantly improved (TI?=?59.0) compared with that of 1 (TI?=?5.5). The structures of these metabolites were elucidated through extensive spectroscopic methods, and the possible biotransformation pathway of 1 by Mucor polymorphosporus was also proposed. Furthermore, the mechanism of the antiproliferative effects against MGC-803 cells of the most potent compound, 2′-Z auraptene A (2), was characterized. Annexin V/PI staining and abnormal expression of apoptosis-related protein suggested that compound 2 induces apoptosis in gastric cancer MGC-803 cells. Therefore, it is possible that compound 2 has the potential to be applied in gastric cancer therapy.
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KEYWORD
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Biotransformation, Mucor polymorphosporus, Terpene coumarin, Human gastric cancer MGC-803 cell line, Apoptosis
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