TY - JOUR
T1 - Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity
T2 - Potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment
AU - Tanida, Satoshi
AU - Mizoshita, Tsutomu
AU - Ozeki, Keiji
AU - Tsukamoto, Hironobu
AU - Kamiya, Takeshi
AU - Kataoka, Hiromi
AU - Sakamuro, Daitoku
AU - Joh, Takashi
PY - 2012
Y1 - 2012
N2 - Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c-Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP-ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity.
AB - Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c-Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP-ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity.
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U2 - 10.1155/2012/862879
DO - 10.1155/2012/862879
M3 - Review article
C2 - 22778941
AN - SCOPUS:84866153536
SN - 2090-1402
VL - 2012
JO - International Journal of Surgical Oncology
JF - International Journal of Surgical Oncology
M1 - 862879
ER -