JNK/p53 mediated cell death response in K562 exposed to etoposide-ionizing radiation combined treatment.
The study of the ability of chemotherapeutic agents and/or ionizing radiation (IR) to induce cell death in tumor cells is essential for setting up new and more efficient therapies against human cancer. Since drug and ionizing radiation resistance is an impediment to successful chemotherapy against cancer, we wanted to check if etoposide/ionizing radiation combined treatment could have a synergic effect to improve cell death in K562, a well-known human erythroleukemia ionizing radiation resistant cell line. In this study, we examined the role played by JNK/SAPK, p53, and mitochondrial pathways in cell death response of K562 cells to etoposide and IR treatment. Our results let us suppose that the induction of cell death, already evident in 15 Gy exposed cells, mainly in 15 Gy plus etoposide, may be mediated by JNK/SAPK pathway. Moreover, p53 is a potential substrate for JNK and may act as a JNK target for etoposide and ionizing radiation. Thus further investigation on these and other molecular mechanisms underlying the cell death response following etoposide and ionizing radiation exposure could be useful to overcome resistance mechanisms in tumor cells.
Sabatini
Nadia
N
Dipartimento di Biomorfologia, Università G. D' Annunzio, Chieti-Pescara, Italy.
Di Giacomo
Viviana
V
Rapino
Monica
M
Rana
Rosalba
R
Garaci
G
G
Giuseppe
Francesco
F
Cataldi
Amelia
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases