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Research Paper
Enhancing TRAIL-Induced Apoptosis by Bcl-XL siRNA
Hongbo Zhu, Wei Guo, Lidong Zhang, John J. Davis, Shuhong Wu, Fuminori Teraishi, Xiaobo Cao, W. Roy Smythe and Bingliang Fang
volume 4 | issue 4
April 2005Pages: 393-397
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We previously found that a change in the balance between mitochondrial pro- and anti-apoptotic proteins caused by ectopic expression of the Bax gene led to increased induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To investigate whether a similar effect can be elicited by down-regulating Bcl-XL, an anti-apoptotic protein, we tested the effects of a small interfering RNA (siRNA) specific for Bcl-XL in TRAIL-resistant cells. The down-regulation of Bcl-XL by siRNA inhibited cell proliferation and sensitized TRAIL-induced apoptosis in human cancer cells with both acquired and intrinsic TRAIL resistance. Combining the Bcl-XL siRNA with TRAIL protein treatment resulted in an increase in the percentage of apoptotic cells and increased cleavage of caspase-8, caspase-9, caspase-3, and PARP. Furthermore, the release of cytochrome c but not Smac from mitochondria was induced by Bcl-XL siRNA alone, and this release was dramatically amplified by combining the Bcl-XL siRNA and TRAIL protein treatment. Together, our data suggest that simultaneous triggering of the death receptor and mitochondrial apoptotic pathways leads to enhanced induction of apoptosis, which makes it potentially useful for the treatment of resistant cancers.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.