Exogenous Morphine Inhibits Human Gastric Cancer MGC-803 Cell Growth by Cell Cycle Arrest and Apoptosis Induction

Caudatin 3-O-β-D-cymaropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (CGII) is one of the C21-steroidal glycosides isolated from the roots ofCynanchum auriculatumROYLE ex WIGHT. This study aimed to determine the cell growth, cell proliferation, and apoptotic cell death of human gastric cancer cells after CGII treatment. MTT assay was used to determine cell growth; fluorescence-activated cell sorting analysis was used to evaluate cell cycle distribution and apoptotic cell death. Immunoblotting was applied for measuring the expression of proteins involved in the cell cycle progression. The activities of caspase-3, -8, and -9 were detected by colorimetric caspase activity assays. CGII inhibited cell growth of human gastric cancer SGC-7901 cells in a concentration- and time-dependent manner. Treatment of SGC-7901 cells with CGII resulted in G1 phase cell cycle arrest, accompanied with decreased expression of cyclin D1 and cyclin-dependent kinases 4 and 6. CGII induced cell apoptosis and activated caspase-3, caspase-8, and caspase-9. In contrast, pan-caspase inhibitor z-VAD-fmk partially abolished the CGII-induced growth inhibition of SGC-7901 cells. In conclusion, CGII inhibits cell growth of human gastric cancer cells by inducing G1 phase cell cycle arrest and caspase-dependent apoptosis cascades.

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Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

Biomolecules ◽

10.3390/biom9080302 ◽

2019 ◽

Vol 9 (8) ◽

pp. 302 ◽

Cited By ~ 10

Author(s):

Xin Zhang ◽

Yao Qin ◽

Zhaohai Pan ◽

Minjing Li ◽

Xiaona Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Protein Expression ◽

Cell Cycle Arrest ◽

Phase Cell ◽

G1 Phase ◽

Therapeutic Effects ◽

Human Gastric Cancer ◽

Expression Levels ◽

Cycle Arrest

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

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