Tea polyphenols induce S phase arrest and apoptosis in gallbladder cancer cells

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.

Apoptosis induced by (di-isopropyloxyphoryl-Trp)2-Lys-OCH3 in K562 and HeLa cells.

According to the method used in our laboratory,our group synthesized (DIPP-Trp)2-Lys-OCH 3. It inhibited the proliferation of K562 and HeLa cells in a dose-and time-dependent manner with an IC 50 of 15.12 and 42.23 microM, respectively. (DIPP-Trp) 2-Lys-OCH3 induced a dose-dependent increase of the G2/M cell population in K562 cells, and S cell population in HeLa cells;the sub-G0 population increased dramatically in both cell lines as seen by PI staining experiments using a FACS Calibur Flow cytometer (BeckmanCoulter,USA). Phosphatidylserine could signi?cantly translocate to the surface of the membrane in (DIPP-Trp)2-Lys-OCH3-treated K562 and HeLa cells.The increase of an early apoptotic population was observed in a dose-dependent manner by both annexin-FITC and PI staining.It was concluded that (DIPP-Trp) 2-Lys-OCH3 not only induced cells to enter into apoptosis,but also affected the progress of the cell cycle.It may have arrested the K562 and HeLa cells in the G 2/M,S phases,respectively.The apoptotic pathway was pulsed at this point,resulting in the treated cells entering into programmed cell death.(DIPP- Trp)-Lys-OCH is a potential anticancer drug that intervenes in the signalling pathway.

Etoposide-induced Smad6 expression is required for the G1 to S phase transition of the cell cycle in CMT-93 mouse intestinal epithelial cells

The inhibitory Smad6 and Smad7 are responsible for cross-talk between TGF-beta/bone morphogenic protein (BMP) signaling and other cellular signaling pathways, as well as negative feedback on their own signaling functions. Although inhibitory Smads are induced by various stimuli, little is known about the stimuli that increase Smad6 transcription, in contrast to Smad7. Here we demonstrate that etoposide, which induces double strand breaks during DNA replication, significantly up-regulates the transcription of the Smad6 gene in CMT-93 mouse intestinal cells by increasing specific DNA binding proteins. In addition, endogenous inhibition of the Smad6 gene by RNAi interference led to transient accumulation of G1 phase cells and reduction in incorporation of bromodeoxyuridine (BrdU). These findings strongly suggest that Smad6 plays a distinct role in the signaling of etoposide-induced DNA damage.

Evaluation of the mutagenic activity of hydroxyurea on the G1-S-G2 phases of the cell cycle: an in vitro study

Hydroxyurea is considered an antineoplastic drug, which also plays an important role in the treatment of sickle cell anemia patients. We evaluated and compared the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal aberrations and mitotic index, respectively, as endpoints. In vitro short-term cultures of lymphocytes were exposed to several concentrations of this drug, at various cell cycle phases. There was a significant increase in the cytotoxicity of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle. Hydroxyurea did not significantly increase chromosome aberrations. There was an S-dependent cytotoxic effect of hydroxyurea, which is expected based on the known activity of hydroxyurea as an inhibitor of ribonucleotide reductase

Mecanismos de ativaçäo do linfócito T e induçäo da leucemia linfoma T do adulto pelo HTLV I / Lymphocyte T activation and adult T lymphoma-leukemia induction by HTLV I

A infecçäo pelo vírus linfotrópico de célula T, tipo I (HTLV I), endêmica em algumas regiöes do mundo, ganha conotaçäo principalmente pelo fato de induzir a leucemia linfoma T do adulto e paraparesia espástica tropical/mielopatia associada ao HTLV I. O conhecimento da fisiopatologia da transformaçäo da célula T auxilia tanto a compreensäo das vias normais de ativaçäo/proliferaçäo do linfócito, como no mecanismo de aparecimento de doenças linfoproliferativas. As estratégias usadas pelo vírus para induzir à proliferaçäo celular afeta o ciclo celular em diferentes estágios e em diferentes vias de sinalizaçäo. Seräo analisadas as principais vias envolvidas nessa questäo e alguns mecanismos de açäo do vírus.

Differential effect of cordycepin on S and G2 phases of cell cycle in plasmodia of Physarum polycephalum Schw.

Effect of pulse treatments of cordycepin, an analog of adenosine, on S and G2 phases of the cell cycle of the mitotically synchronous plasmodia of Physarum polycephalum has been studied. Various concentrations of the drug (50-200 micrograms ml-1) were found to be effective in delaying mitosis by several hours in both the phases. However, there was a significant increase in mitotic delay in those treated during G2. It is suggested that this extra delay during G2 could be due to the transcriptive level inhibition of specific RNA types, such as that of tubulins, whose gene activity is cell cycle regulated and turned on during G2 in Physarum, or alternatively because of a deficiency for ATP and the consequent inhibition of events such as mitotic spindle assembly and phosphorylation of histones.