Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-κB p65 in esophageal carcinoma cells

Possible involvement of Fas/Fas-L synergism

T. L. Liu, H. Shimada, T. Ochiai, T. Shiratori, Sey-En Lin, M. Kitagawa, K. Harigaya, M. Maki, M. Oka, T. Abe, M. Takiguchi, T. Hiwasa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated μ-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-κB p65 and Fas. Since purified m- or μ-calpain degraded NF-κB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-κB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.

Original languageEnglish
Pages (from-to)1025-1037
Number of pages13
JournalApoptosis
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2006
Externally publishedYes

Fingerprint

Peplomycin
Fas Ligand Protein
Calpain
Cells
Carcinoma
Camptothecin
calpastatin
Cytarabine
Mitomycin
Pharmaceutical Preparations
Complementary DNA
Western Blotting
Degradation

Keywords

  • Calpain
  • Esophageal carcinoma
  • Fas
  • NF-κB
  • Peplomycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-κB p65 in esophageal carcinoma cells : Possible involvement of Fas/Fas-L synergism. / Liu, T. L.; Shimada, H.; Ochiai, T.; Shiratori, T.; Lin, Sey-En; Kitagawa, M.; Harigaya, K.; Maki, M.; Oka, M.; Abe, T.; Takiguchi, M.; Hiwasa, T.

In: Apoptosis, Vol. 11, No. 6, 01.06.2006, p. 1025-1037.

Research output: Contribution to journalArticle

Liu, TL, Shimada, H, Ochiai, T, Shiratori, T, Lin, S-E, Kitagawa, M, Harigaya, K, Maki, M, Oka, M, Abe, T, Takiguchi, M & Hiwasa, T 2006, 'Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-κB p65 in esophageal carcinoma cells: Possible involvement of Fas/Fas-L synergism', Apoptosis, vol. 11, no. 6, pp. 1025-1037. https://doi.org/10.1007/s10495-006-6353-y
Liu, T. L. ; Shimada, H. ; Ochiai, T. ; Shiratori, T. ; Lin, Sey-En ; Kitagawa, M. ; Harigaya, K. ; Maki, M. ; Oka, M. ; Abe, T. ; Takiguchi, M. ; Hiwasa, T. / Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-κB p65 in esophageal carcinoma cells : Possible involvement of Fas/Fas-L synergism. In: Apoptosis. 2006 ; Vol. 11, No. 6. pp. 1025-1037.
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abstract = "Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated μ-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-κB p65 and Fas. Since purified m- or μ-calpain degraded NF-κB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-κB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.",
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AU - Shimada, H.

AU - Ochiai, T.

AU - Shiratori, T.

AU - Lin, Sey-En

AU - Kitagawa, M.

AU - Harigaya, K.

AU - Maki, M.

AU - Oka, M.

AU - Abe, T.

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AU - Hiwasa, T.

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AB - Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated μ-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-κB p65 and Fas. Since purified m- or μ-calpain degraded NF-κB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-κB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.

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