Viriditoxin Induces G2/M Cell Cycle Arrest and Apoptosis in A549 Human Lung Cancer Cells

Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTP-binding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to beta-tubulin indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.

The inhibition effects of continuous low dose rate radiation of 125I radioactive seeds on KYSE150 esophageal cancer cells / 中华放射医学与防护杂志

Objective To determine the biological effectiveness of 125I radioactive seeds with continuous low dose rate radiation on the human esophageal cancer cell line KYSE150 in vitro and explore the underlying cellular mechanisms.Methods The cells were divided into three cell groups:control group,single dose radiation group (SDR) and 125I radioactive seeds with continuous low dose rate radiation group (125 I-CLDR).The KYSE150 cells were exposed to radiation of X-ray at a high dose rate of 1.052 Gy/min or 125I radioactive seeds at a low dose rate of 2.77 cGy/h.The responses of KYSE150 cells to two modes of irradiation were evaluated by the colony-forming assay,cell apoptosis as well as cell cycle analysis.Furthermore,the expression levels of γ-H2AX and Bax were detected by Western blot.Results KYSE150 cells were more radiosensitive to 125I-CLDR than SDR.The relative biological effectiveness (RBE) for 125I-CLDR related to SDR was 1.56.Compared with SDR,125I-CLDR yielded more proportions of the early and late apoptosis rate (t =4.07,11.08,P ＜0.05) as well as cells at G2/M phase (t =11.25,P ＜0.05).Moreover,γ-H2AX and Bax expression levels in 125I-CLDR significantly increased compared with SDR.Conclusions Compared with the high dose rate X-ray radiation,the continuous low dose rate radiation of 125I radioactive seeds had stronger inhibition effect on KYSE150 esophageal cancer cells by impairing clonogenic capacity,inducing apoptosis and G2/M cell cycle arrest,and increasing radiosensitivity.

Genistein Induces G2/M Cell Cycle Arrest and Apoptosis in Rat Neuroblastoma B35 Cells; Involvement of p21(waf1/cip1), Bax and Bcl-2

BACKGROUND: The effect of genistein on different types of cells has been investigated. However, its effect on the nervous system is still unclear. The aim of the present work is to explore the effect of genistein on rat neuroblastoma B35 cells. METHODS: The effect of genistein on the proliferation of B35 cells, its cytotoxicity, the cell-cycle distribution, the ultra-structural changes and the induction of apoptosis were determined using MTT assay, LDH assay, Flow-cytometric analysis, transmission electron microscopy and Hoechst staining, respectively. Furthermore, Real-time quantitative RT-PCR and Western blotting were used to examine the transcriptional and post-translational alterations of the G2/M cell-cycle arrest marker cyclin-dependent kinase inhibitor p21(waf1/cip1) and the apoptosis-related genes after genistein treatment. RESULTS: Genistein significantly inhibits cell survival, slightly elevates the release of lactate dehydrogenase and induced apoptosis in B35 cells. Genistein increased the number of cells at S-phase and induced cells to accumulate at the G2/M phase. These G2/M arrested cells are associated with a marked up-regulation of p21(waf1/cip1) at both the mRNA and protein levels. We observed that genistein up-regulates pro-apoptotic Bax with concurrent down-regulation of the anti-apoptotic Bcl-2 protein. CONCLUSION: These observations suggest that the anticancer effect of genistein on B35 neuroblastoma cells is mediated through multiple cellular pathways including G2/M cell-cycle arrest and the induction of apoptosis.