TY - JOUR
T1 - Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells
AU - Martinotti, Simona
AU - Ranzato, Elia
AU - Parodi, Monica
AU - Vitale, Massimo
AU - Burlando, Bruno
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca2+, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.
AB - Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca2+, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.
KW - Cell cycle
KW - Combined therapy
KW - DAPK2
KW - PCR array
KW - REN mesothelioma cells
UR - http://www.scopus.com/inward/record.url?scp=84889596580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84889596580&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2013.10.025
DO - 10.1016/j.taap.2013.10.025
M3 - Article
AN - SCOPUS:84889596580
VL - 274
SP - 35
EP - 41
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
ER -