Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species / 癌症

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.

Effect of ST2325 on cell cycle in erbB2-overexpressing breast cancer MDA-MB-453m1 cells and its mechanism / 中国癌症杂志

Purpose：Effect of ST2325 on cell cycle in erbB2-overexpressing MDA-MB-453m1 cells and its mechanism was investigated.Methods：Cell cycle distribution was examined using flow cytometry. The protein expression was detected with Western blot analysis.Results：Under concentrations of 0,6.25,12.5,25.0,50.0,100 μmol/L，the percentrages of G0/G1 in MDA-MB-453m1 were 48.62%, 48.83%, 49.59%, 52.18%, 61.0%,83.96%; the percentages of S were 33.34%, 33.16%, 32.78%,30.77%,25.62%,7.08%;the percentages of G2M were 18.04%, 18.01%,17.63%,17.05%,13.38%,8.96%.After MDA-MB-453m1 cells were treated with different concentrations of ST2325 for 24 hours, Western blot assay showed up-regulation of p27 protein expression and decrease of hyperphosphorylated Rb and cyclin D1 protein expression .Activation of MAPK and AKT in MDA-MB-453m1 was markedly inhibited by ST2325.Conclusions：ST2325 induces G1 arrest in erbB2-overexpressing MDA-MB-453m1 cancer cells. G1 arrest is associated with p27 upregulation,decrease of cyclinD1 protein and hyperphosphorylated Rb.

Preparation and application of monoclonal antibodies to recombinant human IFN alpha / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To prepare and apply monoclonal antibodies (McAb) against recombinant human interferon alpha (rHu IFN-alpha).</p><p><b>METHODS</b>Five cell lines (2E9, 4G1, 2A7, 2C9, 4G10) secreting McAbs against rHu IFN-alpha were established by hybridoma technique.</p><p><b>RESULTS</b>All the cell lines secreted monoclonal antibodies stably. Functions of secreting antibodies of the five cell lines lasted for 6 months in BALB/c mice and 8 months in cell culture. The specificity of antibody was constant. The Ig subclasses of the McAbs were IgG1. Anti-IFN McAb affinity purification column was prepared by coupling the anti IFN-alpha McAb to Sepharose 4B. The combining rate reached was higher than 95%.</p><p><b>CONCLUSIONS</b>The highest purification efficiency was obtained by using 4G10 column.</p>