Abstract
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 of Cynanchum auriculatum ROYLE 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.
Highlights
Gastric cancer (GC) is a complex and enigmatic disorder noted for marked global variations in etiology, incidence, natural course, and management [1]
MTT assay was used to determine the effect of CGII on the proliferation of SGC-7901 cells and lactate dehydrogenase (LDH) activity of culture medium was measured to determine the cell damage induced by CGII
Deregulation of cell cycle checkpoints is a hallmark of cancer cells ; inhibiting cell proliferation by inducing cell cycle arrest in cancer cells is an effective strategy for cancer therapy [14, 15]
Summary
Gastric cancer (GC) is a complex and enigmatic disorder noted for marked global variations in etiology, incidence, natural course, and management [1]. Natural products are very important compounds in the area of cancer chemotherapy due to their excellent pharmacological activities and low toxicity. There are numerous natural plants used for clinical cancer therapy in traditional Chinese medicine. C21-steroidal glycosides, are of considerable interest for pharmacological purpose. Previous studies have found that the C21-steroidal glycosides isolated from “Baishouwu” protect hepatocytes and neurons as well as gastric cells from toxicities [3,4,5]. Caudatin 3-O-β-D-cymaropyranosyl-(1 → 4)-β-Doleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)β-D-cymaropyranoside (CGII) (Figure 1) is a C21-steroidal glycosides first isolated in 1995 [10]. We determined the cell growth, cell cycle distribution, and cell death pathways in human gastric cancer SGC-7901 cells after CGII treatment
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