CAS enhances chemotherapeutic drug-induced p53 accumulation and apoptosis: Use of CAS for high-sensitivity anticancer drug screening

Ching Fong Liao, Shue Fen Luo, Chin Shaw Stella Tsai, Tang Yi Tsao, Shun Liang Chen, Ming Chung Jiang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cells attacked by cytotoxic toxins may express apoptosis-related proteins such as p53 to kill themselves, so as not to affect surrounding healthy cells. These apoptosis-related proteins are also crucial for inducing apoptosis of tumor cells in cancer chemotherapy. CSE1L/CAS is a cellular apoptosis susceptibility protein that plays important roles in mediating cell apoptosis induced by various cytotoxic toxins and chemotherapeutic drugs. Our studies showed that CAS over-expression increased p53 accumulation and apoptosis induced by 5-fluorouracil, doxorubicin, cisplatin, and tamoxifen in HT-29 cancer cells. A method based on coexpression of CAS with green fluorescence protein (GFP) was developed for high-sensitivity anticancer drug screening. Cancer cells transfected with CAS- and GFP-expressing vectors or the control and GFP-expressing vectors were grown on 96-well microplates, treated with compounds to be screened, and detected with a microplate fluorescence reader. GFP fluorescence decreased following cancer cell death induced by the anticancer compounds. CAS transfection enhanced the cytotoxicities of anticancer compounds and therefore increased the decline in GFP fluorescence. Thus, anticancer compounds could be identified more sensitively. Our study indicates that CAS is an important p53 and apoptosis regulator and may be used for high-throughput anticancer drug screening as well as cytotoxic toxin assays.

Original languageEnglish
Pages (from-to)771-776
Number of pages6
JournalToxicology Mechanisms and Methods
Volume18
Issue number9
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Anticancer drugs
  • Apoptosis
  • CAS
  • Green fluorescence protein
  • High-throughput screening
  • p53

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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