Caspase-8 gene transduction augments radiation-induced apoptosis in DLD-1 cells

Biochemical and Biophysical Research Communications
Hiroaki UchidaHirofumi Hamada

Abstract

Caspase-8 is a member of the cysteine protease family that plays a critical role in death receptor-mediated apoptosis. We previously demonstrated that adenovirally transduced caspase-8 efficiently induced apoptosis in tumor cells (Shinoura et al. (2000) Hum. Gene Ther. 11, 1123-1137). However, to ensure safety in clinical applications some devise for minimization of the dose of adenoviral vector required for sufficient antitumor effect is needed. In this study, we evaluated the proapoptotic effect in DLD-1 colon cancer cells of a combination of low-dose infection with an adenoviral vector expressing caspase-8 and X-ray irradiation. Under these conditions, X-ray irradiation strongly induced apoptosis whereas irradiation without transduction only had a trace proapoptotic effect. Overexpression of bcl-xL strongly blocked the activation of caspase-8 and induction of apoptosis, suggesting that adenovirally transduced caspase-8 was activated at a point downstream of mitochondria. This combination strategy may be a useful modality for gene therapy of colorectal cancer.

Citations

Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brigette B Y MaLillian L Siu
Apr 14, 2006·Neoplasia : an International Journal for Oncology Research·Yuying LiuMichael G Rosenblum
Jul 21, 2005·Technology in Cancer Research & Treatment·T RobsonD G Hirst

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