TY - JOUR
T1 - The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death
AU - Stendel, Ruediger
AU - Biefer, Hector Rodriguez Cetina
AU - Dékány, Gabriela Marta
AU - Kubota, Hisashi
AU - Münz, Christian
AU - Wang, Sheng
AU - Mohler, Hanns
AU - Yonekawa, Yasuhiro
AU - Frei, Karl
PY - 2009/2/16
Y1 - 2009/2/16
N2 - The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.
AB - The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.
KW - Apoptosis
KW - Autophagy
KW - Brain tumor
KW - Glioblastoma
KW - Glioma
KW - Programmed cell death
UR - http://www.scopus.com/inward/record.url?scp=61649096836&partnerID=8YFLogxK
U2 - 10.4161/auto.5.2.7404
DO - 10.4161/auto.5.2.7404
M3 - Article
C2 - 19066471
AN - SCOPUS:61649096836
SN - 1554-8627
VL - 5
SP - 194
EP - 210
JO - Autophagy
JF - Autophagy
IS - 2
ER -