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Apoptosis of Cancer Cells: Down Regulation of DNA Replication and Glycolipid Biosynthesis
Author(s) -
Ma Rui,
Boyle Patrick John,
Cho Yoonie,
Basu Manju,
Banerjee Sipra,
Basu Subhash
Publication year - 2006
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.20.4.a120-d
Subject(s) - apoptosis , cancer cell , microbiology and biotechnology , chemistry , cancer research , biology , cancer , biochemistry , genetics
In cancer cells the components of the apoptotic pathway exist but not always activated unless given anti‐cancer agents. Human breast carcinoma MCF‐7, MDA‐468, and SKBR‐3 and ovarian carcinoma SKOV‐3 were treated with the anti‐cancer agents cis ‐platin (Pol‐α inhibitor/DNA crosslinker; 10–80 μM) or L‐PPMP (glycosyltransferase GlcT inhibitor; 1–8 μM). These drugs initiated apoptosis in a dose‐dependent manner as measured by morphological changes and the phosphatidylserine relocalization by fluorescent dye PSS‐380 binding. Both caspase‐8 and ‐3 were activated in cells treated with ci s‐platin as detected by Western Blot. Caspase‐9 and ‐3 activation is being studied in the cells treated with L‐PPMP. The extrinsic and intrinsic pathways were suggested for treatment with cis ‐platin and L‐PPMP, respectively. Little is known about the stability of the replisome during apoptosis. The DNA helicase‐III was characterized as a part of the replisome complex from carcino‐embryonic cells. Helicase activity was quantitated using a novel (ROME) assay developed in our lab that measures the release of oligonucleotides (20–60 nt) from radiolabeled DNA. Dose‐dependent decreases in DNA pol‐α (80%) and DNA helicase (60%) activities were observed upon treatment with cis ‐platin. A sharp decrease of activities of the glycolipid sialyltransferases SAT‐2 and SAT‐4 was observed in the cells treated with L‐PPMP compared to cis ‐platin. The expression of ER‐α short and long forms in the MCF‐7 cells treated with these anti‐cancer drugs is under study.