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REGULATION OF APOPTOSIS IN BREAST CANCER CELLS INDUCED BY CIS‐PLATIN AND L‐PPMP
Author(s) -
Ma Rui,
Cho Yoonie,
Crowford Gabriel,
Pineda Denise,
Thomas Christopher,
Banerjee Sipra,
Basu Subhash
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a260-b
Subject(s) - apoptosis , signal transduction , ceramide , biology , gliotoxin , gene , enzyme , effector , microbiology and biotechnology , chemistry , cancer research , biochemistry , immunology , aspergillus fumigatus
The overall objective of our study is to elucidate the regulation of glycolipid glycosyltransferases (GSL‐GLTs) and the related signal transduction during apoptosis (induced by cis ‐platin and L‐PPMP) in human breast carcinoma cells (SKBR‐3, MCF‐7, MDA‐468). Abnormal expression of any particular GSL‐GLT may lead to a distorted sequence. A recently characterized trafficking of ceramide and GD3 ganglioside into mitochondria has revealed a novel function of this GSL as a death effector ( Glycoconj J . 2004; 20 (5):–30). Different signal transduction pathways could be involved in apoptosis, such as MAPKs, Akt, NF‐kB and caspases cascades. Little is known about the regulation of GSL‐GLTs during apoptosis. We tested different GSL‐GLT activities with the treatment of anti‐cancer reagent L‐PPMP (1 to 16μM) or cis ‐Platin (10 to 200μM). The enzyme inhibition is not due to the presence of any free inducers. The Golgi membranes were isolated and tested for GSL‐GLT activities (GalT‐4, GalT‐5, SAT‐1, SAT‐2, SAT‐3 and SAT‐4). Sharp decrease of some of these GSL‐GLT activities (GalT‐4, GalT‐5 and SAT‐4) during apoptosis suggests that perhaps these enzymes are either inactivated or down‐regulated in their expression. Deregulation of replication complexes in the presence of cis ‐platin was also observed ( Glycoconj J . 2006; 23 (3–4):–87). Further studies on gene expression using GLT gene chip ‐ arrays are in progress.