Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.
Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology ; Caspase 8/metabolism ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Neoplastic Stem Cells ; Paclitaxel/pharmacology ; alpha-Tocopherol/*pharmacology

Metabolic flux analysis is a very powerful tool to understand CO2 fixation and light energy utilization of microalgae during photoautotrophic cultivation. A comprehensive network structure for the autotrophic growth of Synechococcus sp. PCC7942 was proposed, and the carbon and energetic metabolism under different incident light intensity was investigated based on metabolic flux analysis in this paper. These results showed that CO2 fixation was the main energy and reducing potential trap which accounted for 85% and 70% of the total energy and reducing potential consumption respectively. We also found that the cell yield and the maximum cell yield based on ATP synthesis were maintained 2.80 g/mol and 2.97 g/mol respectively under the appointed incident intensity. But the cell yield on absorbed light energy their corresponding energy conversion efficiency were descended with the increasing of incident intensity.
Carbon ; metabolism ; Carbon Cycle ; Carbon Dioxide ; metabolism ; Cell Culture Techniques ; Energy Metabolism ; drug effects ; Light ; Photochemical Processes ; Synechococcus ; growth & development ; metabolism

OBJECTIVETo explore the antineoplastic effect in vitro of earthworm coelomic fluid (ECF)on growth inhibition and its mechanism for the tumor cell lines Siha, SW480, Colo205 and PC12.

METHODSMTT colorimetric assay, flow cytometry and morphological analysis were used to test its antitumor activity on tumor cell lines and normal cell line Cos7 in vitro.

RESULTSECF can inhibit the cell growth of Siha, SW480, Colo205, PC12 and Cos7. But different tumor cell lines showed different sensitivity.

CONCLUSIONEFC can significantly inhibit the proliferation of tumor cells in vitro by inducing tumor cells apoptosis.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Body Fluids ; chemistry ; COS Cells ; Cell Growth Processes ; drug effects ; Cell Line ; Cell Line, Tumor ; Cercopithecus aethiops ; Oligochaeta ; chemistry ; PC12 Cells ; Rats

BACKGROUNDSam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line.

METHODSBy using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometric analyses were performed to investigate the Sam68 functions.

RESULTSA slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells.

CONCLUSIONSThe proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; physiology ; Animals ; B-Lymphocytes ; cytology ; immunology ; physiology ; Binding Sites ; genetics ; Blotting, Western ; Cell Cycle ; physiology ; Cell Death ; physiology ; Cell Growth Processes ; drug effects ; physiology ; Cell Line, Tumor ; Culture Media, Serum-Free ; pharmacology ; Mutation ; genetics ; Phosphorylation ; Proline ; genetics ; RNA-Binding Proteins ; genetics ; metabolism ; physiology ; Receptors, Antigen, B-Cell ; immunology ; physiology ; Signal Transduction ; drug effects ; physiology ; Tyrosine ; metabolism

OBJECTIVETo investigate the effects of Nocardia rubra cell wall skeleton (Nr-CWS) on the HeLa cell line, one of the cell lines of human cervical cancer, infected with HPV.

METHODSHPV-infected HeLa (HPV 18-positive cells) cultured in vitro were divided into two groups: the experiment group and control group. Nr-CWS was added to the experiment group and PBS to the control. The growth and proliferation of HeLa cells were detected with MTT and flow cytometry technology. Inhibitive effect of HeLa transplanted tumor was investigated in Scid mice.

RESULTSThe growth of HeLa cells in the experimental group was apparently decreased compared with that of the control. The results of flow cytometry demonstrated that more HeLa cells were transferred into quiescent phase in the experimental group than that in the control. While less in the proliferative phase, both of the volume and weight of HeLa transplanted tumor with drug-added group were less than those of control group.

CONCLUSIONThe Nocardia rubra cell wall skeleton is a potiental growth inhibitor and inducer of apoptosis of cervical cancer cells in vitro and may provide a new way in prevention or supplementary management of anti-human papilloma virus.

Animals ; Cell Growth Processes ; drug effects ; Cell Survival ; drug effects ; Cell Wall Skeleton ; pharmacology ; therapeutic use ; Female ; Flow Cytometry ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Mice ; Mice, SCID ; Nocardia ; metabolism ; Papillomaviridae ; physiology ; Uterine Cervical Neoplasms ; pathology ; prevention & control ; virology ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effect of estrogen (E2), progesterone(P4), and paclitaxel (taxol) on the growth of primary human ovarian cancer cells in vitro and the expression of Drosha.

METHODSHuman ovarian cancer cells were treated with estrogen, progesterone or in combination with paclitaxel in vitro. The inhibition rate of ovarian cancer cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis rate and cell cycle were determined by FACS analysis. The relative abundence of Drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.

RESULTSThe inhibition rate of the estrogen group, progesterone group, paclitaxel group, E2(+)Taxol group, P4(+)Taxol group was (31.53 ± 8.21)%, (25.22 ± 15.50)%, (46.71 ± 4.25)%, (69.46 ± 3.71)%, and (47.35 ± 39.02)%, respectively, significantly higher than that of the control group (0%, P<0.05 for all). Relative to the ER (-) in ovarian cancer cells,Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+) Taxol group,and P4(+)Taxol group was 1.62 ± 0.10,1.60 ± 0.10,1.75 ± 0.16,1.95 ± 0.20, and 1.53 ± 0.06, respectively, significantly higher than that of the control group (1.00, P<0.05 for all). Relative to the ER (+)in ovarian cancer cells,the Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+)taxol group, and P4(+)Taxol group was 1.03 ± 0.14, 1.60 ± 0.09, 1.75 ± 0.16, 1.60 ± 0.10, 1.53 ± 0.06, respectively except estrogen group, significantly higher than that of the control group (1.00, P<0.05). Relative to the ER (-) in ovarian cancer cells, the Drosha protein expression levels of the control group, estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) Taxol group were 0.25 ± 0.05, 0.87 ± 0.30, 0.85 ± 0.38, 1.30 ± 0.21, 1.75 ± 0.83, 1.62 ± 0.82, respectively, with a significant difference between the experimental groups and the control group (P<0.05). Relative to the ER(+)ovarian cancer cells, the Drosha protein expression levels in the estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) taxol group, were 0.28 ± 0.16, 0.85 ± 0.38, 1.30 ± 0.21, 0.94 ± 0.18, and 1.62 ± 0.82, respectively except estrogen group, significantly higher than that of the control group (0.25 ± 0.05, P<0.05 for all).

CONCLUSIONSEstrogen and progesterone in combination with paclitaxel can inhibit the growth of human ovarian cancer cells in vitro, and affect the cell apoptosis rate. Estrogen and taxol can alter the cell cycle. Estrogen and progesterone combined with paclitaxel show tumor suppressing or sensitizing effect through upregulated Drosha expression, and are associated with the estrogen receptor expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Cell Cycle ; Cell Growth Processes ; drug effects ; Cell Line, Tumor ; Coloring Agents ; Drug Therapy, Combination ; Estrogens ; pharmacology ; Female ; Humans ; In Vitro Techniques ; Ovarian Neoplasms ; chemistry ; drug therapy ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Progesterone ; pharmacology ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; metabolism ; Ribonuclease III ; genetics ; metabolism ; Tetrazolium Salts ; Thiazoles ; Up-Regulation