Activation of caspases and apoptosis in response to low-voltage electric pulses

Noriaki Matsuki, Motohiro Takeda, Takuji Ishikawa, Aki Kinjo, Tomoaki Hayasaka, Yohsuke Imai, Takami Yamaguchi

研究成果: ジャーナルへの寄稿学術論文査読

21 被引用数 (Scopus)


Few studies have examined apoptosis induced by low-voltage electric pulses (LVEPs). LVEP-induce changes in membrane potential that are below the membrane breakdown threshold and increase membrane permeability without electroporation (pore formation) through the transport of extracellular substances via phagocytosis. We demonstrated that propidium iodide uptake and apoptosis increased in accordance with the duration and number of LVEPs in B16 cells, which showed relatively good viability under mild electric field conditions. We showed that LVEP-induced apoptosis was achieved through caspase-8 and -9 activation and subsequent caspase-3 activation. Long-duration LVEPs caused only mild cell damage, such that the apoptosis ratio (apoptosis/total cell death) in electric pulse-treated cells was similar to that in non-treated control cells. To assess the relative degree of caspase dependency in LVEP-induced apoptosis, the apoptosis rate and caspase-3 activity were analyzed using a pan-caspase inhibitor (Z-VAD-FMK). Z-VAD-FMK treatment inhibited, but did not abolish, LVEP-induced apoptosis, indicating that caspases other than caspase-3 participate in this pathway. Moreover, LVEP treatment inhibited cell growth, suggesting that LVEP treatment may be a valuable anticancer therapy. Although the mechanism of LVEP-induced apoptosis remains unclear, it may be related to dysfunctional membrane transport of Ca2+ and other extracellular substances involved in caspase activation.

ジャーナルOncology Reports
出版ステータス出版済み - 2010 5月


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