Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand

Rishindra M. Reddy, Wilson S. Tsai, M. Firdos Ziauddin, Jingtong Zuo, George W. Cole, Justin B. Maxhimer, Bingliang Fang, David S. Schrump, Dao M. Nguyen

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression. This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein. Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit. Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL. Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while not affecting normal cells. The mechanisms underlying this effect might include both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells. These findings provide a rationale for development of Ad/gTRAIL-based therapy for thoracic malignancies.

Original languageEnglish (US)
Pages (from-to)883-891
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume128
Issue number6
DOIs
StatePublished - Dec 1 2004

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Adenoviridae
Cisplatin
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Neoplasms
Green Fluorescent Proteins
TNF-Related Apoptosis-Inducing Ligand
Transgenes
Inhibitory Concentration 50
Fluorescence
Cultured Cells
Flow Cytometry
Thorax
Enzyme-Linked Immunosorbent Assay
Cell Line

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand. / Reddy, Rishindra M.; Tsai, Wilson S.; Ziauddin, M. Firdos; Zuo, Jingtong; Cole, George W.; Maxhimer, Justin B.; Fang, Bingliang; Schrump, David S.; Nguyen, Dao M.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 128, No. 6, 01.12.2004, p. 883-891.

Research output: Contribution to journalArticle

Reddy, Rishindra M. ; Tsai, Wilson S. ; Ziauddin, M. Firdos ; Zuo, Jingtong ; Cole, George W. ; Maxhimer, Justin B. ; Fang, Bingliang ; Schrump, David S. ; Nguyen, Dao M. / Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand. In: Journal of Thoracic and Cardiovascular Surgery. 2004 ; Vol. 128, No. 6. pp. 883-891.
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AU - Zuo, Jingtong

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AU - Nguyen, Dao M.

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