Endogenously released Smac is insufficient to mediate cell death of human lung carcinoma in response to etoposide

Experimental Cell Research
Babett BartlingB Zhivotovsky

Abstract

Cytotoxic agents eliminate tumor cells via different mechanisms including apoptosis, although this process is not equally efficient in all kinds of cancer cells. Thus, small cell lung carcinomas (SCLCs) are more sensitive than non-small cell lung carcinomas (NSCLCs) to therapy-induced killing. During apoptosis, several apoptogenic proteins release from the mitochondria. Among these proteins is Smac/DIABLO. Overexpression of Smac effectively potentiates apoptosis by neutralizing the caspase-inhibitory function of the inhibitors of apoptosis proteins (IAPs). However, the physiological relevance of endogenously released Smac in the promotion of malignant cell death is still unclear. Analysis of a panel of human lung cancer cell lines revealed that there is no altered Smac expression in NSCLC and SCLC that might initially impair the drug-induced cell death. Upon engagement of the mitochondrial pathway of apoptosis, etoposide provoked cytosolic accumulation of Smac along with cytochrome c and loss of the mitochondrial membrane potential. Most of these events as well as nuclear apoptotic changes required caspase activation in SCLC, but not in NSCLC. Unexpectedly, pan-caspase inhibition had no effect on Smac release. Co-treatment of S...Continue Reading

Citations

Oct 5, 2007·Neuromolecular Medicine·Veronika StokaDale E Bredesen
Mar 15, 2014·International Journal of Oncology·Erika MoravcikovaNorbert Pauk
Sep 17, 2005·American Journal of Respiratory Cell and Molecular Biology·Babett BartlingAndreas Simm
Oct 19, 2005·Journal of Cancer Research and Clinical Oncology·Evzen KrepelaPavel Selinger
Apr 6, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kristina Viktorsson, Rolf Lewensohn
Aug 26, 2006·The International Journal of Biochemistry & Cell Biology·Santiago Rello-VaronaAngeles Villanueva
Jun 20, 2006·Experimental Cell Research·Andrey KropotovBoris Zhivotovsky
Apr 8, 2006·Experimental Gerontology·Babett BartlingAndreas Simm

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis