The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) and genistein is effective in inhibiting pancreatic cancer growth

Fumiaki Nozawa, Atsushi Itami, Murat Saruc, Min Kim, Jens Standop, Kathleen S. Picha, Kenneth H Cowan, Parviz M. Pour

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objectives: Our previous studies have shown that, contrary to many other human pancreatic adenocarcinoma cell lines, AsPC1 cells are resistant to the apoptotic effect of the tumor necrosis factor-related apoptosis-inducing ligand, also called Apo2L (TRAIL/Apo2L). In our in vitro studies, the combination of TRAIL/Apo2L and protein synthesis inhibitor, genistein, but not genistein alone, was, however, effective in inducing apoptosis in AsPC1 cells. In the present study, we examined the effect of TRAIL/Apo2L with genistein on the growth of ASPC1 cells in vitro and in vivo. Methods: Mice with orthotopically transplanted AsPC1 cells were treated either with TRAIL/Apo2L, Genistein (Gen) or a combination of both (TRAIL/Apo2L + Gen) for 14 days. After 14 days, the size and weight of the tumors were registered and the apoptosis of the tumor cells were determined by the TUNEL method. In vitro, the effect of combination treatment on cytotoxicity was assessed by MTT assay and apoptosis was assessed by DAPI staining. FADD, caspase 3, and PARP proteins were determined by Western blot. Results: No toxic side effects were observed in either group. The tumor volume was significantly smaller and the apoptotic ratio was higher in the TRAIL + Gen group than in the other 2 groups. The apoptotic effect was associated with the caspase-3 activation. Z-VAD-FMK partially inhibited apoptosis by TRAIL + Gen. Conclusions: These results indicate that the combination of TRAIL/Apo2L with genistein presents a promising therapeutic approach for the treatment of pancreatic cancer. Further detail investigations are needed, however, to verify the mechanisms of this combination therapy.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalPancreas
Volume29
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

Genistein
Pancreatic Neoplasms
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Growth
Tumor Burden
Caspase 3
TNF-Related Apoptosis-Inducing Ligand
Protein Synthesis Inhibitors
Poisons
In Situ Nick-End Labeling
Adenocarcinoma
Western Blotting
Staining and Labeling
Cell Line
Therapeutics

Keywords

  • Apoptosis
  • Genistein
  • Pancreatic cancer
  • TRAIL/Apo2L

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) and genistein is effective in inhibiting pancreatic cancer growth. / Nozawa, Fumiaki; Itami, Atsushi; Saruc, Murat; Kim, Min; Standop, Jens; Picha, Kathleen S.; Cowan, Kenneth H; Pour, Parviz M.

In: Pancreas, Vol. 29, No. 1, 01.07.2004, p. 45-52.

Research output: Contribution to journalArticle

Nozawa, Fumiaki ; Itami, Atsushi ; Saruc, Murat ; Kim, Min ; Standop, Jens ; Picha, Kathleen S. ; Cowan, Kenneth H ; Pour, Parviz M. / The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) and genistein is effective in inhibiting pancreatic cancer growth. In: Pancreas. 2004 ; Vol. 29, No. 1. pp. 45-52.
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abstract = "Objectives: Our previous studies have shown that, contrary to many other human pancreatic adenocarcinoma cell lines, AsPC1 cells are resistant to the apoptotic effect of the tumor necrosis factor-related apoptosis-inducing ligand, also called Apo2L (TRAIL/Apo2L). In our in vitro studies, the combination of TRAIL/Apo2L and protein synthesis inhibitor, genistein, but not genistein alone, was, however, effective in inducing apoptosis in AsPC1 cells. In the present study, we examined the effect of TRAIL/Apo2L with genistein on the growth of ASPC1 cells in vitro and in vivo. Methods: Mice with orthotopically transplanted AsPC1 cells were treated either with TRAIL/Apo2L, Genistein (Gen) or a combination of both (TRAIL/Apo2L + Gen) for 14 days. After 14 days, the size and weight of the tumors were registered and the apoptosis of the tumor cells were determined by the TUNEL method. In vitro, the effect of combination treatment on cytotoxicity was assessed by MTT assay and apoptosis was assessed by DAPI staining. FADD, caspase 3, and PARP proteins were determined by Western blot. Results: No toxic side effects were observed in either group. The tumor volume was significantly smaller and the apoptotic ratio was higher in the TRAIL + Gen group than in the other 2 groups. The apoptotic effect was associated with the caspase-3 activation. Z-VAD-FMK partially inhibited apoptosis by TRAIL + Gen. Conclusions: These results indicate that the combination of TRAIL/Apo2L with genistein presents a promising therapeutic approach for the treatment of pancreatic cancer. Further detail investigations are needed, however, to verify the mechanisms of this combination therapy.",
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T1 - The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) and genistein is effective in inhibiting pancreatic cancer growth

AU - Nozawa, Fumiaki

AU - Itami, Atsushi

AU - Saruc, Murat

AU - Kim, Min

AU - Standop, Jens

AU - Picha, Kathleen S.

AU - Cowan, Kenneth H

AU - Pour, Parviz M.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - Objectives: Our previous studies have shown that, contrary to many other human pancreatic adenocarcinoma cell lines, AsPC1 cells are resistant to the apoptotic effect of the tumor necrosis factor-related apoptosis-inducing ligand, also called Apo2L (TRAIL/Apo2L). In our in vitro studies, the combination of TRAIL/Apo2L and protein synthesis inhibitor, genistein, but not genistein alone, was, however, effective in inducing apoptosis in AsPC1 cells. In the present study, we examined the effect of TRAIL/Apo2L with genistein on the growth of ASPC1 cells in vitro and in vivo. Methods: Mice with orthotopically transplanted AsPC1 cells were treated either with TRAIL/Apo2L, Genistein (Gen) or a combination of both (TRAIL/Apo2L + Gen) for 14 days. After 14 days, the size and weight of the tumors were registered and the apoptosis of the tumor cells were determined by the TUNEL method. In vitro, the effect of combination treatment on cytotoxicity was assessed by MTT assay and apoptosis was assessed by DAPI staining. FADD, caspase 3, and PARP proteins were determined by Western blot. Results: No toxic side effects were observed in either group. The tumor volume was significantly smaller and the apoptotic ratio was higher in the TRAIL + Gen group than in the other 2 groups. The apoptotic effect was associated with the caspase-3 activation. Z-VAD-FMK partially inhibited apoptosis by TRAIL + Gen. Conclusions: These results indicate that the combination of TRAIL/Apo2L with genistein presents a promising therapeutic approach for the treatment of pancreatic cancer. Further detail investigations are needed, however, to verify the mechanisms of this combination therapy.

AB - Objectives: Our previous studies have shown that, contrary to many other human pancreatic adenocarcinoma cell lines, AsPC1 cells are resistant to the apoptotic effect of the tumor necrosis factor-related apoptosis-inducing ligand, also called Apo2L (TRAIL/Apo2L). In our in vitro studies, the combination of TRAIL/Apo2L and protein synthesis inhibitor, genistein, but not genistein alone, was, however, effective in inducing apoptosis in AsPC1 cells. In the present study, we examined the effect of TRAIL/Apo2L with genistein on the growth of ASPC1 cells in vitro and in vivo. Methods: Mice with orthotopically transplanted AsPC1 cells were treated either with TRAIL/Apo2L, Genistein (Gen) or a combination of both (TRAIL/Apo2L + Gen) for 14 days. After 14 days, the size and weight of the tumors were registered and the apoptosis of the tumor cells were determined by the TUNEL method. In vitro, the effect of combination treatment on cytotoxicity was assessed by MTT assay and apoptosis was assessed by DAPI staining. FADD, caspase 3, and PARP proteins were determined by Western blot. Results: No toxic side effects were observed in either group. The tumor volume was significantly smaller and the apoptotic ratio was higher in the TRAIL + Gen group than in the other 2 groups. The apoptotic effect was associated with the caspase-3 activation. Z-VAD-FMK partially inhibited apoptosis by TRAIL + Gen. Conclusions: These results indicate that the combination of TRAIL/Apo2L with genistein presents a promising therapeutic approach for the treatment of pancreatic cancer. Further detail investigations are needed, however, to verify the mechanisms of this combination therapy.

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KW - Pancreatic cancer

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