cyclin-d1 and Carcinoma--Lewis-Lung

Esculetin was identified to inhibit cell proliferation and induce apoptosis or cell cycle arrest in several cancer cell lines. However, the effect of esculetin on lung cancer remains elusive.. The anti-proliferative role of esculetin in murine Lewis lung carcinoma (LLC) cells was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. BALB/c mice were subcutaneously injected with LLC cells to investigate the inhibitory effect of esculetin on the growth of lung cancer xenograft. Invasive ability was detected in esculetin treated and untreated LLC cells by transwell assay. The association between esculetin and Wnt/β-catenin signaling, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), was confirmed by testing the expression of c-myc, Cyclin D1 and NF-κB using Western blot.. Esculetin treatment in LLC cells led to significant decrease of cell proliferation in a time- and dose-dependent manner. After injection of LLC cells into mice, reduced size and weight of tumors were observed in esculetin treated mice compared to untreated mice. However, no difference in cell invasion was observed between the treated and untreated LLC cells. Notably decreased expression of c-myc, Cyclin D1 and NF-κB were observed in LLC cells with esculetin treatment compared to untreated cells.. Esculetin plays an inhibitory role in the growth of lung cancer by down-regulating c-myc, Cyclin D1 and NF-κB.

Topics: Animals; Apoptosis; beta Catenin; Carcinoma, Lewis Lung; Cell Proliferation; Coloring Agents; Cyclin D1; Down-Regulation; Female; Heterografts; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; NF-kappa B; Salivary alpha-Amylases; Tetrazolium Salts; Thiazoles; Tumor Stem Cell Assay; Umbelliferones; Wnt Proteins

Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells.. To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms.. A549 cells were treated with 10~320 μg/ml Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) . Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured.. Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at 20 μg/ml, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro.. Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Lewis Lung; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Down-Regulation; Humans; Lung Neoplasms; Mice; Mice, Inbred C57BL; Proliferating Cell Nuclear Antigen; Quercetin; Tumor Suppressor Protein p53; Up-Regulation

To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression.. Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewis-bearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method.. Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G0/G1 phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G0/G1 phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyclin D1 in tumor tissues were decreased as compared with the untreated and control groups.. Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.

Topics: Animals; Antineoplastic Agents; Bone Marrow Cells; Carcinoma, Lewis Lung; Cell Cycle; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclophosphamide; Drugs, Chinese Herbal; Leukopenia; Male; Mice; Mice, Inbred C57BL; Phytotherapy; Random Allocation

Lovastatin, the drug used for the treatment of hypercholesterolemia, has previously been reported to exert antitumor activity in experimental murine models. Butyrate and butyric acid derivatives are well known to induce differentiation and apoptosis of tumour cells and also have recently gained acceptance as potential anticancer agents. In this study, we examined the antitumor effects of the combination of lovastatin and butyrate or its prodrug tributyrin in vitro and in vivo against a murine Lewis lung carcinoma (3LL). This combination therapy showed synergistic antitumor activity against 3LL cells in vitro. These effects were at least in part due to apoptosis induction that occurred after 12 hr of incubation with lovastatin and butyrate and was preceded by changes in cell cycle distribution of treated cells and expression of p21, p53 and cyclin D1. Remarkably, a systemic treatment of syngeneic mice inoculated with 3LL cells with both drugs resulted in significant tumour growth retardation.

Topics: Animals; Antineoplastic Agents; Blotting, Western; Carcinoma, Lewis Lung; Cell Cycle; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Drug Synergism; Drug Therapy, Combination; Female; Flow Cytometry; Formazans; Lovastatin; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Tetrazolium Salts; Triglycerides; Tumor Suppressor Protein p53