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Euphorbia helioscopia L. is a traditional Chinese medicine; recently research found that its ethyl acetate extract (EAE) plays an important role on tumor cell proliferation, apoptosis, invasion, and metastasis in vitro. But the effect of EAE for tumor cells in vivo has not been reported. To explore the inhibitory effect of EAE and molecular mechanism on hepatocellular carcinoma (HCC) SMMC-7721 cells in vivo, we utilized the nude mouse xenograft model of HCC. Treated with EAE (50, 100, and 200 μg/mL), the volume of xenograft was measured during the entire process of EAE treatment. In EAE treatment group, the volume of xenograft was significantly reduced compared with the control group (P < 0.05) and the protein expressions of CyclinD1, bcl-2, and MMP-9 were reduced, while those of bax, caspase-3, and nm23-H1 were increased. A significant change trend with increasing EAE concentrations has presented, compared with controls. Moreover, the ultrastructural morphology of xenografts showed significant changes, including nuclear pyknosis and chromatin condensation, We found that EAE could effectively inhibit tumor growth, induce apoptosis, and inhibit tumor invasion and metastasis in vivo; it is suggested that EAE is a potential candidate for as a new anticancer agent.

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer. This study was designed to test the hypothesis that honokiol enhances the radiosensitivity of cancer cells with mismatch repair defect (HCT116) compared with those that are mismatch repair proficient (HCT116-CH3). We first determined that the combination of honokiol and γ-irradiation treatment resulted in dose-dependent inhibition of proliferation and colony formation in both cell lines. However, the effects were more pronounced in HCT116 cells. Similarly, the combination induced higher levels of apoptosis (caspase 3 activation, Bax to Bcl2 ratio) in the HCT116 cells compared with HCT116-CH3 cells. Cell cycle analyses revealed higher levels of dead cells in HCT116 cells. The combination treatment reduced expression of cyclin A1 and D1 and increased phosphorylated p53 in both cell lines, although there were significantly lower amounts of phosphorylated p53 in the HCT116-CH3 cells, suggesting that high levels of hMLH1 reduce radiosensitivity. These data demonstrate that honokiol is highly effective in radiosensitizing colorectal cancer cells, especially those with a mismatch repair defect.

We investigated whether X-ray radiation induced apoptosis of the proliferative ependymal cells (ECs) in adult rats with spinal cord injury (SCI) and the effect of X-ray radiation on the proliferative activities of ECs. A rat model with SCI was developed and used to determine the proliferation and apoptosis of ECs in the spinal cords after X-ray exposure. TUNEL assay and BrdU incorporation were used to detect apoptosis and proliferation respectively. We found that there were few TUNEL-positive cells in proliferative ependymal zone (EZ) after SCI except at the epicenter, and approximately half of the irradiated ECs became TUNEL-positive. However, these radiated ECs did not lose their proliferative activity until 1 week later and started to decrease rapidly after 1 week. The observation suggested that only part of ECs were sensitive to radiation and the nonsensitive cells continued their mitosis process. These findings indicated that X-ray exposure of the rats with SCI in early stage induced apoptosis of the proliferative ECs and partially inhibited their proliferative activities.

Abstract: The expression of alpha-fetoprotein (AFP), a tumor-associated antigen, is silenced in normal adult hepatocyte but reactivated in human hepatocellular carcinoma (HCC). To investigate the roles of AFP in the regulation of cell growth, we silenced AFP expression in the HCC cell line Huh7 by transfection of specific Stealth™ RNAi. After the transfection for 48h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 46.15%, and the number of cells undergoing early apoptosis was significantly increased to 63.93%. Inhibition of AFP expression also resulted in an increased in Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and activation of caspase-3. The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via dysfunction of the p53/Bax/cytochrome c/caspase-3 signaling pathway in AFP-producing HCC cell line. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment. [Copyright &y& Elsevier]

Oxovanadium complexes, particularly vanadyl (IV) derivatives with hybrid ligands of Schiff base and polypyridyl, have been demonstrated to possess great anticancerous therapeutic efficacy. However, most of the studies on the activity of these oxovanadium complexes have mainly focused on in vitro studies, and animal studies in vivo are extremely scarce. Based on the antitumor test results of four novel oxovanadium complexes in our previous work, this work further conducted a comprehensive antitumor activity study in vitro and in vivo on VO(hntdtsc)(NPIP), which owned the strongest inhibitory activity in vitro on multiple tumor cell proliferation. The cellular mechanism study suggested that VO(hntdtsc)(NPIP) inhibited the cell proliferation via arresting the cell cycle at G0/G1 phase through the p16-cyclin D1-CDK4-p-Rb pathway and inducing cell apoptosis through mitochondrial-dependent apoptosis pathway on HeLa cells. Inconsistent with the effects in vitro , VO(hntdtsc)(NPIP) significantly inhibited the growth of tumor and induced the apoptosis of cancer cells in mice xenograft models according to the results of nude mice in vivo image detection, H&E pathological examination, and immunohistochemical detection of p16/Ki-67 protein expression. Collectively, all the results, particularly studies in vivo, demonstrated that VO(hntdtsc)(NPIP) hold a potential to be the lead compound and further to be an anticervical cancer drug. [ABSTRACT FROM AUTHOR]