cotylenin-a and Retinoblastoma

Retinoblastoma, a childhood cancer of the retina, is caused by inactivation of the tumor suppressor gene retinoblastoma (RB). Cotylenin A (CN-A), a novel fusicoccane-diterpene glycoside, accelerates the differentiation of several types of myeloid cell lines and is a candidate for a new type of anticancer therapeutic agent with this effect. However, whether CN-A has the same effect on retinoblastoma cells is unknown. We studied the response of two retinoblastoma cell lines, Y-79 and WERI-Rb-1, to CN-A.. We studied the response of two retinoblastoma cell lines to CN-A with respect to cell growth, apoptosis, morphology, mRNA, protein expression analysis of specific genes (N-myc, cyclin-dependent kinase inhibitor 1A [P21], paired box gene 6 [PAX6], and rhodopsin [RHO]), and activity of three PAX6 promoters (P0, P1, and Palpha).. CN-A inhibited cell proliferation and induced apoptosis via caspase activity in the two retinoblastoma cell lines. In addition, CN-A induced mRNA expression of P21, PAX6, and RHO and protein expression of P21. In Y-79 cells, PAX6 P1 promoter was activated by CN-A. In WERI-Rb-1 cells, PAX6 P0, P1, and Palpha promoter were activated by CN-A. CN-A decreased mRNA and protein expression of N-myc in two retinoblastoma cell lines.. The responses of retinoblastoma cells to CN-A include inhibition of cell growth, induction of apoptosis, and the potential to change neuroblastoma characteristics of retinoblastoma cells.

Topics: Apoptosis; Caspases; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Diterpenes; Down-Regulation; Exons; Eye Proteins; Gene Expression; Histone Deacetylase Inhibitors; Homeodomain Proteins; Humans; Paired Box Transcription Factors; PAX6 Transcription Factor; Promoter Regions, Genetic; Repressor Proteins; Retinoblastoma; Rhodopsin; RNA, Messenger; Up-Regulation