Radiosensitization of solid tumors by Z-VAD, a pan-caspase inhibitor

Luigi Moretti, Woon Kim Kwang, Kwang Jung Dae, Christopher D. Willey, Bo Lu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Despite recent advances in the management of breast and lung cancer, novel treatment strategies are still needed to further improve patient outcome. The targeting of cell death pathways has therefore been proposed to enhance therapeutic ratio in cancer. In this study, we examined the in vitro and in vivo effects of Z-VAD, a broad-spectrum caspase inhibitor, on breast and lung cancer in association with radiation. Using clonogenic assays, we observed that Z-VAD markedly radiosensitized breast and lung cancer cells, with a radiation dose enhancement ratio of 1.31 (P < 0.003). For both models, the enhanced tumor cytotoxicity was associated with induction of autophagy. Furthermore, we found that administration of Z-VAD with radiation in both breast and lung cancer xenograft produced a significant tumor growth delay compared with radiation alone and was well tolerated. Interestingly, Z-VAD also had dramatic antiangiogenic effect when combined with radiation both in vitro and in vivo and thus represents an attractive anticancer therapeutic strategy. In conclusion, this preclinical study supports the therapeutic potential of Z-VAD as a radiosensitizer in breast and lung cancer. This study also suggests caspase inhibition as a promising strategy to enhance the therapeutic ratio of radiation therapy in solid tumors. Therefore, clinical trials are needed to determine the potential of this combination therapy in cancer patients.

Original languageEnglish (US)
Pages (from-to)1270-1279
Number of pages10
JournalMolecular Cancer Therapeutics
Volume8
Issue number5
DOIs
StatePublished - May 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Radiosensitization of solid tumors by Z-VAD, a pan-caspase inhibitor'. Together they form a unique fingerprint.

  • Cite this