Oxaliplatin triggers necrosis as well as apoptosis in gastric cancer SGC-7901 cells

Biochemical and Biophysical Research Communications
Ping WuLinjie Zhang

Abstract

Intrinsic apoptotic pathway is considered to be responsible for cell death induced by platinum anticancer drugs. While in this study, we found that, necrosis is an indispensable pathway besides apoptosis in oxaliplatin-treated gastric cancer SGC-7901 cells. Upon exposure to oxaliplatin, both apoptotic and necrotic features were observed. The majority of dead cells were double positive for Annexin V and propidium iodide (PI). Moreover, mitochondrial membrane potential collapsed and caspase cascades were activated. However, ultrastructural changes under transmission electron microscope, coupled with the release of cellular contents, demonstrated the rupture of the plasma membrane. Oxaliplatin administration did not stimulate reactive oxygen species (ROS) production and autophagy, but elevated the protein level of Bmf. In addition, receptor interacting protein 1 (RIP1), but not receptor interacting protein 3 (RIP3) and its downstream components participated in this death process. Necrostatin-1 (Nec-1) blocked oxaliplatin-induced cell death nearly completely, whereas z-VAD-fmk could partially suppress cell death. Oxaliplatin treatment resulted in poly(ADP-ribose) polymerase-1 (PARP-1) overactivation, as indicated by the increase of...Continue Reading

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Citations

Jan 1, 2016·Toxicon : Official Journal of the International Society on Toxinology·Xiaosheng QuWei Shu
Oct 16, 2015·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·BaoZhong ShanXin Xu
Dec 2, 2017·British Journal of Pharmacology·Rachel M McQuadeKulmira Nurgali
May 4, 2020·The American Journal of the Medical Sciences·Yanli NieFuxiang Zhou

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