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Apoptotic mechanism of novel anticancer agents is mediated by MAPKs in breast cancer cells
Author(s) -
McLean Lancelot Stuart,
Brantley Eileen
Publication year - 2013
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.27.1_supplement.1105.3
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , apoptosis , phosphorylation , cancer research , signal transduction , mechanism of action , chemistry , aryl hydrocarbon receptor , cancer , cancer cell , pharmacology , microbiology and biotechnology , medicine , biology , biochemistry , in vitro , gene , transcription factor
Aminoflavone and 5F203 are two potential candidate anticancer agents. While their mechanism of action is not fully elucidated, aspects of their anticancer activity differ from currently available agents. Even though the aryl hydrocarbon receptor (AhR) signaling pathway is the primary known mechanism of action of these agents, other signaling pathways may also be involved. Our objective was to investigate the apoptotic mechanism of AF and 5F 203 in MDA‐MB‐468 and T47D breast cancer cell lines. One group of cells were treated time dependently with vehicle or AF or 5F203. A second group of cells were pretreated with MAPK inhibitors, followed by AF or 5F203. Cells were then analyzed for MAPK phosphorylation, apoptosis and ROS formation. Our results showed that AF and 5F203 induced phosphorylation of ERK1/2, JNK1/2 and p38 in MDA‐MB‐468 and T47D breast cancer cell lines. We also showed that ERK, JNK and p38 inhibitors attenuated the apoptotic effect of AF and 5F203. Additionally, AF and 5F203‐induced ROS production was decreased by the MAPK inhibitors. These results suggest that the MAPK signaling pathway is involved in the mechanism of action of AF and 5F203 in MDA‐MB‐468 and T47D cells. These studies were supported in part by the School of Dentistry and Medicine at Loma Linda University