Apoptosis of Breast Cancer Cells by L‐PPMP and cis‐Platin: Translational and Transcriptional Regulation of Glycosyltransferase Genes

Abstract

Apoptotic effects of anti‐cancer agents (glycolipid biosynthesis inhibitor L‐PPMP, DNA biosynthesis inhibitor cis‐Platin) in human breast cancer cells (MCF‐7, MDA‐468, and SKBR‐3) were identified with techniques including phase contrast microscopy, DNA laddering, and the flopping of PS with PSS‐380 fluorescent dye studies. Using a new fluorescent Dye (AKS‐0) in the presence of these two apoptotic reagents, we observed a time‐dependent scrambling of membranes of mitochondria, ER, and Golgi bodies. SA‐LeX (neolacto‐series glycolipids) is distributed mostly on the outer lamella of plasma membranes of human breast and colon metastatic cells. Although exact functions of these glycoconjugates are not yet known, direct analyses of these glyco‐molecules suggest they alter their structures during the onset of oncogenic processes. A time‐dependent down‐regulation of glycosyltransferase (GLTs) activities involved in the biosynthesis of SA‐LeX [GalT‐4, GalT‐5, and FucT‐3] and gangliosides [SAT‐4 and SAT‐2] was observed. By using novel DNA‐microarrays specifically designed for screening 359 Glyco‐related genes, transcriptional up‐regulation of several GLTs involved in the biosyntheses of Sialo‐LeX and Sialo‐Lea (cancer cell surface antigens) was observed. Down‐regulation of GLT activities and up‐regulation of some GLT mRNA suggest a tight regulation of these enzymes by signal transduction pathways.