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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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