cyclin-d1 and artenimol

Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood.. The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway.. We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling.. DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.

Topics: Animals; Artemisinins; Carcinogenesis; Cell Cycle Checkpoints; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Female; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Invasiveness; Prognosis; Signal Transduction; Stomach; Stomach Neoplasms; Xenograft Model Antitumor Assays

Lung cancer is the most common cause of cancer-related death in the world. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC); non small cell lung carcinoma (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma, Non small cell lung carcinoma accounts for about 80% of the total lung cancer cases. Dihydroartemisinin (DHA) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of DHA on cell growth and proliferation in lung cancer cells remain to be elucidated. Here, we demonstrate that DHA inhibited cell proliferation in the A549 lung cancer cell line through suppression of the AKT/Gsk-3β/cyclin D1 signaling pathway. DHA significantly inhibited cell proliferation of A549 cells in a concentration and time dependent manner as determined by MTS assay. Flow cytometry analysis demonstrated that DHA treatment of A549 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. These results suggest that DHA is a potential natural product for the treatment of lung cancer.

Topics: Antineoplastic Agents; Apoptosis; Artemisinins; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Flow Cytometry; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Immunohistochemistry; Lung Neoplasms; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Signal Transduction

Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cancer BxPC-3 and AsPC-1 cells in vitro and subcutaneous BxPC-3 xenograft tumors in mice. The MTT assay was used to evaluate cell viability, and flow cytometry and laser scanning confocal microscopy were used to detect apoptosis, for cultured cells. Pancreatic tumors were established by subcutaneous injection of BxPC-3 cells in nude BALB/c mice, and DHA was administered intraperitoneally to the mice. The size of tumors was monitored and they were harvested after the mice had been killed. Tumor sections were immunostained with an anti-Ki-67 Ab to assess the proliferation index, or stained with TUNEL to evaluate in-situ cell apoptosis. The gene expression in cells and tumors was evaluated by western blot analysis. In the cultured cells, DHA inhibited cell viability, downregulated the expression of proliferating cell nuclear antigen and cyclin D1, and upregulated p21(WAF1/CIP1); and induced apoptosis by reducing the ratio of Bcl-2/Bax and increasing the activation of caspase-9, in a dose-dependent manner. Similarly, in mice bearing BxPC-3 xenograft tumors, administration of DHA inhibited tumor growth in a dose-dependent manner, and modulated tumoral gene expression consistent with the in-vitro observations. This study indicates that DHA may be a potent and promising agent to combat pancreatic cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Artemisinins; bcl-2-Associated X Protein; Caspase 9; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Dose-Response Relationship, Drug; Humans; Ki-67 Antigen; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Xenograft Model Antitumor Assays