Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

被引:14
|
作者
Jin, Shan [1 ]
Shi, Kuan [1 ]
Liu, Liu [2 ]
Chen, Yu [2 ]
Yang, Guangzhong [1 ]
机构
[1] South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Hubei, Peoples R China
[2] South Cent Univ Nationalities, Coll Chem & Mat Sci, Wuhan 430074, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
xanthones; Garcinia xanthochymus; apoptosis; HepG2; caspase; Bcl-2; family; MMPs; MATRIX-METALLOPROTEINASE (MMP)-2; ALPHA-MANGOSTIN; HYPERICUM-JAPONICUM; PROTEIN EXPRESSION; SIGNALING PATHWAY; CANCER-CELLS; INHIBITORS; BCL-2; MMP-9;
D O I
10.3390/ijms20194803
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.
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页数:14
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