Epigenetic regulation of microRNA expression in renal cell carcinoma.

The underlying mechanisms of microRNA deregulation in cancer cells include epigenetic modifications, which play a crucial role in carcinogenesis. We demonstrate that numerous microRNAs are induced in renal cell carcinoma cell lines after treatment with inhibitors of the DNA-methyltransferase (5-aza-2'-deoxycytidine) and the histone-deacetylase (suberoylanilide hydroxamic acid). We provide evidence that enrichment of H3 and H3K18 acetylation at the miR-9 promoter is causative for re-expression, while DNA hypermethylation remains unchanged.

Antiproliferative and apoptosis inducing effects of indirubin-3'-monoxime in renal cell cancer cells.

Objectives: Indirubin-3'-monoxime, which is a selective and potent inhibitor of cyclin-dependent kinases (CDKs) has shown preclinical activity in several human cancer cells. This study investigated if indirubin-3'-monoxime can induce apoptosis and tumor cell death in 3 human (A498, CAKI-1, CAKI-2) and 1 murine renal cell cancer (RENCA) cell line.

Methods: The growth inhibitory and apoptosis induction properties were evaluated by EZ4U, a cytotoxic assay and by flow cytometry of annexin-V/PI staining during treatment with doses ranging from 5.

Indirubin-3'-monoxime, a CDK inhibitor induces growth inhibition and apoptosis-independent up-regulation of survivin in transitional cell cancer.

In traditional Chinese Medicine, the preparation Danggui Longhui Wan has been used for years in the treatment of chronic myelocytic leukemia. The compound indirubin has been shown to be the active constituent. A cell permeable derivative, indirubin-3'-monoxime, is a selective and potent inhibitor of cyclin-dependent kinases (cdk).

Flavopiridol, an inhibitor of cyclin-dependent kinases, induces growth inhibition and apoptosis in bladder cancer cells in vitro and in vivo.

Flavopiridol is a semi-synthetic flavone analog of the alkaloid, rohitukine, a compound from an Indian tree, Dysoxylum binectariferum. It has been shown to inhibit cyclin-dependent kinases (CDKs), causing cell cycle arrest and growth inhibition. Flavopiridol is reported to have cytotoxic activity against a wide range of cancer cell lines and has demonstrated its efficacy in several clinical trials.

Superantigen-activated mononuclear cells induce apoptosis in transitional cell carcinoma.

Background: Superantigens are among the most potent T-cell mitogens known. Since T-cell activation and T-cell-derived cytokines play a role in the immune response associated with intravesical Bacillus Calmette-Guerin (BCG) application, this study was initiated to explore the fundamental aspects of a potential new immunomodulatory therapy for superficial bladder cancer. Since Superantigen-induced cytotoxicity is mediated by apoptosis, the effects of SEB (staphylococcal enterotoxin B)-Superantigen-activated PBMC (peripheral blood mononuclear cells) on bladder cancer cells were evaluated with regard to Fas/Fas-ligand-based interactions.

Carboxyamido-triazole (CAI) reverses the balance between proliferation and apoptosis in a rat bladder cancer model.

Carboxyamido-triazole (CAI) is an orally bioavailable calcium influx and signal transduction inhibitor that has been shown to be anti-invasive, anti-angiogenic and anti-metastatic in different human tumors including transitional cell carcinoma. This study was undertaken to further evaluate the activity of CAI in a rat bladder cancer model. A transitional cell carcinoma (TCC) was chemically induced by intravesical installation of methyl-nitrosurea (MNU) in the bladder of female Fischer 344 rats.

Preclinical evaluation of superantigen (staphylococcal enterotoxin B) in the intravesical immunotherapy of superficial bladder cancer.

Superantigens are potent activators of T lymphocytes; therefore, their characteristics can be exploited in diseases where immunomodulation is known to be effective. In this study, we evaluated a new approach for the intravesical therapy of superficial bladder cancer. We investigated in coculture experiments if staphylococcal enterotoxin B (SEB)-activated PBMCs are able to induce apoptosis in human transitional cell carcinoma (TCC) cells.

Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2.

Pro- and anti-apoptotic factors and intracellular signaling pathways are targets for therapeutic development of anticancer agents. Carboxyamido-triazole (CAI) is an inhibitor of transmembrane calcium influx and intracellular calcium-requiring signal transduction pathways. The present study investigates the effects of CAI on human transitional cancer cell (TCC) viability and apoptosis, and evaluates whether apoptotic resistance may be overcome pharmacologically.