Paeoniflorin inhibits growth of human colorectal carcinoma HT 29 cells in vitro and in vivo
Department of Pharmaceutical Science, Guangzhou Medical University, Guangzhou 510182, China.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association (Impact Factor: 2.9). 02/2012; 50(5):1560-7. DOI: 10.1016/j.fct.2012.01.035
The aim of the therapy of human malignancies is the inhibition of cell proliferation and/or induction of apoptosis. In present experiment, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of paeoniflorin (PF), isolated from the paeony root, against colorectal cancer. In vitro, cell growth assay obviously showed the inhibition of tumor cell growth in a dose-dependent manner. Flow cytometry analysis showed that PF could mainly have the cell cycle arrest at G1, which is associated with DNA damage and activation of p53/14-3-3 zeta (ζ). The pro-apoptotic effect of PF was demonstrated by Annexin V-PI staining, and activation of caspase-3 and caspase-9 by Western immunoblotting. In vivo, the results showed that positive cells of PCNA in PF and docetaxel-treated group was decreased to 30% and 15% compared with control group of tumors, respectively. But apoptosis cells in PF- and docetaxel treated groups studied by TUNEL is increased to 40 ± 1.2% and 30 ± 1.5% compared with 24 ± 2.3% in negative control, respectively. Furthermore, the efficiency of tumor-bearing mice treated by PF was superior to docetaxel in vivo. Overall, PF may be an effective chemopreventive agent against colorectal cancer HT29, and the mechanism could be mediated via an regulation of p53/14-3-3ζ.
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ABSTRACT: Prostaglandin E2 (PGE2) has been shown to play an important role in tumor development and progression. PGE2 mediates its biological activity by binding any one of four prostanoid receptors (EP1 through EP4). The present study was designed to determine the role of the EP2 receptor during the proliferation and apoptosis of human HepG2 and SMMC-7721 hepatoma cell lines and the effect of paeoniflorin, a monoterpene glycoside. The proliferation of HepG2 and SMMC-7721 cells was determined by methyl thiazolyl tetrazolium after exposure to the selective EP2 receptor agonists butaprost and paeoniflorin. Apoptosis of HepG2 and SMMC-7721 cells was also quantified by flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression levels of Bcl-2 and Bax were quantified by western blotting and immunohistochemistry. The expression of the EP2 receptor and cysteine-aspartic acid protease (caspase)-3 was determined by western blotting. Butaprost significantly increased proliferation in HepG2 and SMMC-7721 cells. Paeoniflorin significantly inhibited the proliferation of HepG2 and SMMC-7721 cells stimulated by butaprost at multiple time points (24, 48, and 72 h). Paeoniflorin induced apoptosis in HepG2 and SMMC-7721 cells, which was quantified by annexin-V and propidium iodide staining. Our results indicate that the expression of the EP2 receptor and Bcl-2 was significantly increased, whereas that of Bax and cleaved caspase-3 was decreased in HepG2 and SMMC-7721 cells after stimulation by butaprost. Paeoniflorin significantly decreased the expression of the EP2 receptor and Bcl-2 and increased Bax and caspase-3 activation in HepG2 and SMMC-7721 cells on addition of butaprost. Our results show that the PGE2 receptor subtype EP2 may play a vital role in the survival of both HepG2 and SMMC-7721 cells. Paeoniflorin, which may be a promising agent in the treatment of liver cancer, induced apoptosis in hepatocellular carcinoma cells by downregulating EP2 expression and also increased the Bax-to-Bcl-2 ratio, thus upregulating the activation of caspase-3.
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ABSTRACT: Cordycepin is known to have many pharmacological effects such as anti-tumorigenic, anti-inflammatory and anti-angiogenic activity. However, cordycepin induced apoptosis through the DR3 pathway in human colon cancer cells has not been studied. The effect of cordycepin on anti-proliferation was investigated in this study. Cordycepin significantly inhibited cell viability in a dose and time-dependent manner. Cordycepin increased sub G1 and G2/M phase arrest on HT-29 cells at the concentration of 100μM, whereas cordycepin at 200μM and 400μM increased G1 phase arrest. Cordycepin induced apoptosis in HT-29 cells in a dose-dependent manner as detected by Hoechst and Annexin V-FITC staining. Intracellular ROS levels were higher in cordycepin treated cells as compared to control cells. The protein related to apoptosis was determined by antibody array. p53 and Bax expression increased treatment with cordycepin for 18h. DR3, caspase-8, caspase-1, cleaved caspase-3 and cleaved PARP expression increased. These finding suggest that the cordycepin induces apoptosis through the DR3 pathway in human colon cancer HT-29. These findings suggest that cordycepin should be evaluated further as a therapeutic agent in human colon cancer.
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