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Sodium nitroprusside enhances TRAIL-induced apoptosis via a mitochondria-dependent pathway in human colorectal carcinoma CX-1 cells

Oncogene volume 20, pages 1476–1485 (2001)Cite this article

Abstract

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo-2L) is a recently characterized member of the family of programmed cell death-inducing ligands that includes TNF-α and CD95L (FasL). It is well known that TRAIL binds to the death signaling receptors, DR4 and DR5, and initiates the TRAIL death pathway. Activation of this pathway, mediated through a caspase cascade, causes apoptosis. In this study, we hypothesized that oxidative stress facilitates TRAIL-induced apoptosis by promoting caspase activity through cytochrome c release from mitochondria. Human colorectal carcinoma CX-1 cells were treated with various concentrations of TRAIL (12.5–200 ng/ml) and/or sodium nitroprusside (SNP; 0.03–1 mM) for 12 h. SNP, a nitric oxide donor, which had little toxic effect by itself, enhanced TRAIL-induced cytotoxicity. For example, TRAIL-induced apoptosis (200 ng/ml) was increased by a factor of 2.5-fold in the presence of 1 mM SNP. The combined treatment also caused an increase in cytochrome c release, caspase-3 activity, and PARP cleavage. Overexpression of Bcl-2 completely blocked the SNP-promoting effects, but only moderately inhibited TRAIL-induced apoptosis. Similar results were observed in the presence of hydrogen peroxide or peroxynitrite. Taken together, the present studies suggest that SNP enhances TRAIL-induced cytotoxicity by facilitating the mitochondria-mediated caspase signal transduction pathway.

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Abbreviations

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

SNP:

sodium nitroprusside

TNF-α:

tumor necrosis factor α

PARP:

poly(ADP-ribose) polymerase

DTT:

dithiothreitol

HEPES:

N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid]

PAGE:

polyacrylamide gel electrophoresis

SDS:

sodium dodecyl sulfate

FasL:

Fas ligand

FADD:

Fas-associated death domain

NO:

nitric oxide

PVDF:

polyvinylidine difluoride

ECL:

enhanced chemiluminescence

EDTA:

ethylenediaminetetraacetic acid

EGTA:

Ethylenebisoxyethylenenitrilotetraacetic acid

PMSF:

phenylmethylsulfonyl fluoride

KCN:

potassium ferricyanide

FLIP:

Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein

FAP-1:

Fas-associated phosphatase-1.

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Acknowledgements

This research was supported by NCl Grants CA48000, CA-64139, NIH GM44100 and DOD DAMD17-99-1-9442 grants.

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Authors and Affiliations

  1. Department of Pharmacology and Cancer Institute, School of Medicine, University of Pittsburgh, Pittsburgh, 15213, Pennsylvania, PA, USA

    Yong J Lee, Kun H Lee & Young K Song

  2. Department of Pathology, Wayne State University School of Medicine, Detroit, 48201, Michigan, MI, USA

    Hyeong-Reh Choi Kim

  3. Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas, 78284, TX, USA

    J Milburn Jessup

  4. Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, PA, USA

    Dai-Wu Seol & Timothy R Billiar

  5. Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, PA, USA

    Tae-Hyoung Kim

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Lee, Y., Lee, K., Kim, HR. et al. Sodium nitroprusside enhances TRAIL-induced apoptosis via a mitochondria-dependent pathway in human colorectal carcinoma CX-1 cells. Oncogene 20, 1476–1485 (2001). https://doi.org/10.1038/sj.onc.1204225

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