N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model

Yasue Ishii-Osai, Toshiharu Yamashita, Yasuaki Tamura, Noriyuki Sato, Akira Ito, Hiroyuki Honda, Kazumasa Wakamatsu, Shosuke Ito, Eiichi Nakayama, Masae Okura, Kowichi Jimbow

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Abstract

Background: N-propionyl-4- S-cysteaminylphenol (NPr-4- S-CAP) is selectively incorporated into melanoma cells and degrades them. However, it remains unclear whether NPr-4- S-CAP can induce cell death associated with the induction of host immune responses and tumor suppression in vivo. Objective: To examine the molecular mechanism of NPr-4- S-CAP-mediated cytotoxicity toward melanoma cells and to test whether NPr-4- S-CAP can suppress transplanted primary and secondary B16F1 melanomas. Methods: Cytotoxicity and apoptosis of melanoma cells were assessed by cell counting, flow cytometry, and detection of reactive oxygen species (ROS) and apoptotic molecules. NPr-4- S-CAP-associated host immunity was studied using a B16F1 mouse melanoma model through the application of CD4- and CD8-specific antibodies and tetramer assay. Results: NPr-4-S-CAP suppressed growth of pigmented melanoma cells associated with an increase of intracellular ROS, activation of caspase 3 and DNA fragmentation, suggesting that NPr-4-S-CAP mediated ROS production, eliciting apoptosis of melanoma cells. Growth of transplanted B16F1 melanomas was inhibited after the consecutive intratumoral injections of NPr-4-S-CAP, and the tumor growth after rechallenge of B16F1 was significantly suppressed in the treated mice. This suppression occurred when the treated mice were given the anti-CD4 antibody, but not the anti-CD8 antibody. Tetramer assay demonstrated increased TYRP-2-specific CD8 + T cells in the lymph node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice. Conclusions: These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells through ROS production and generates CD8 + cell immunity resulting in the suppression of rechallenged B16F1 melanoma.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalJournal of Dermatological Science
Volume67
Issue number1
DOIs
Publication statusPublished - Jul 1 2012

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T-cells
Tumors
Melanoma
Reactive Oxygen Species
Apoptosis
T-Lymphocytes
Cytotoxicity
Antibodies
Assays
Neoplasms
Bearings (structural)
Flow cytometry
Cell death
Caspase 3
Chemical activation
Anti-Idiotypic Antibodies
Immunity
Growth
Molecules
N-propionyl-4-S-cysteaminylphenol

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model. / Ishii-Osai, Yasue; Yamashita, Toshiharu; Tamura, Yasuaki; Sato, Noriyuki; Ito, Akira; Honda, Hiroyuki; Wakamatsu, Kazumasa; Ito, Shosuke; Nakayama, Eiichi; Okura, Masae; Jimbow, Kowichi.

In: Journal of Dermatological Science, Vol. 67, No. 1, 01.07.2012, p. 51-60.

Research output: Contribution to journalArticle

Ishii-Osai, Y, Yamashita, T, Tamura, Y, Sato, N, Ito, A, Honda, H, Wakamatsu, K, Ito, S, Nakayama, E, Okura, M & Jimbow, K 2012, 'N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model', Journal of Dermatological Science, vol. 67, no. 1, pp. 51-60. https://doi.org/10.1016/j.jdermsci.2012.04.009
Ishii-Osai, Yasue ; Yamashita, Toshiharu ; Tamura, Yasuaki ; Sato, Noriyuki ; Ito, Akira ; Honda, Hiroyuki ; Wakamatsu, Kazumasa ; Ito, Shosuke ; Nakayama, Eiichi ; Okura, Masae ; Jimbow, Kowichi. / N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model. In: Journal of Dermatological Science. 2012 ; Vol. 67, No. 1. pp. 51-60.
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abstract = "Background: N-propionyl-4- S-cysteaminylphenol (NPr-4- S-CAP) is selectively incorporated into melanoma cells and degrades them. However, it remains unclear whether NPr-4- S-CAP can induce cell death associated with the induction of host immune responses and tumor suppression in vivo. Objective: To examine the molecular mechanism of NPr-4- S-CAP-mediated cytotoxicity toward melanoma cells and to test whether NPr-4- S-CAP can suppress transplanted primary and secondary B16F1 melanomas. Methods: Cytotoxicity and apoptosis of melanoma cells were assessed by cell counting, flow cytometry, and detection of reactive oxygen species (ROS) and apoptotic molecules. NPr-4- S-CAP-associated host immunity was studied using a B16F1 mouse melanoma model through the application of CD4- and CD8-specific antibodies and tetramer assay. Results: NPr-4-S-CAP suppressed growth of pigmented melanoma cells associated with an increase of intracellular ROS, activation of caspase 3 and DNA fragmentation, suggesting that NPr-4-S-CAP mediated ROS production, eliciting apoptosis of melanoma cells. Growth of transplanted B16F1 melanomas was inhibited after the consecutive intratumoral injections of NPr-4-S-CAP, and the tumor growth after rechallenge of B16F1 was significantly suppressed in the treated mice. This suppression occurred when the treated mice were given the anti-CD4 antibody, but not the anti-CD8 antibody. Tetramer assay demonstrated increased TYRP-2-specific CD8 + T cells in the lymph node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice. Conclusions: These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells through ROS production and generates CD8 + cell immunity resulting in the suppression of rechallenged B16F1 melanoma.",
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T1 - N-propionyl-4-S-cysteaminylphenol induces apoptosis in B16F1 cells and mediates tumor-specific T-cell immune responses in a mouse melanoma model

AU - Ishii-Osai, Yasue

AU - Yamashita, Toshiharu

AU - Tamura, Yasuaki

AU - Sato, Noriyuki

AU - Ito, Akira

AU - Honda, Hiroyuki

AU - Wakamatsu, Kazumasa

AU - Ito, Shosuke

AU - Nakayama, Eiichi

AU - Okura, Masae

AU - Jimbow, Kowichi

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Background: N-propionyl-4- S-cysteaminylphenol (NPr-4- S-CAP) is selectively incorporated into melanoma cells and degrades them. However, it remains unclear whether NPr-4- S-CAP can induce cell death associated with the induction of host immune responses and tumor suppression in vivo. Objective: To examine the molecular mechanism of NPr-4- S-CAP-mediated cytotoxicity toward melanoma cells and to test whether NPr-4- S-CAP can suppress transplanted primary and secondary B16F1 melanomas. Methods: Cytotoxicity and apoptosis of melanoma cells were assessed by cell counting, flow cytometry, and detection of reactive oxygen species (ROS) and apoptotic molecules. NPr-4- S-CAP-associated host immunity was studied using a B16F1 mouse melanoma model through the application of CD4- and CD8-specific antibodies and tetramer assay. Results: NPr-4-S-CAP suppressed growth of pigmented melanoma cells associated with an increase of intracellular ROS, activation of caspase 3 and DNA fragmentation, suggesting that NPr-4-S-CAP mediated ROS production, eliciting apoptosis of melanoma cells. Growth of transplanted B16F1 melanomas was inhibited after the consecutive intratumoral injections of NPr-4-S-CAP, and the tumor growth after rechallenge of B16F1 was significantly suppressed in the treated mice. This suppression occurred when the treated mice were given the anti-CD4 antibody, but not the anti-CD8 antibody. Tetramer assay demonstrated increased TYRP-2-specific CD8 + T cells in the lymph node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice. Conclusions: These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells through ROS production and generates CD8 + cell immunity resulting in the suppression of rechallenged B16F1 melanoma.

AB - Background: N-propionyl-4- S-cysteaminylphenol (NPr-4- S-CAP) is selectively incorporated into melanoma cells and degrades them. However, it remains unclear whether NPr-4- S-CAP can induce cell death associated with the induction of host immune responses and tumor suppression in vivo. Objective: To examine the molecular mechanism of NPr-4- S-CAP-mediated cytotoxicity toward melanoma cells and to test whether NPr-4- S-CAP can suppress transplanted primary and secondary B16F1 melanomas. Methods: Cytotoxicity and apoptosis of melanoma cells were assessed by cell counting, flow cytometry, and detection of reactive oxygen species (ROS) and apoptotic molecules. NPr-4- S-CAP-associated host immunity was studied using a B16F1 mouse melanoma model through the application of CD4- and CD8-specific antibodies and tetramer assay. Results: NPr-4-S-CAP suppressed growth of pigmented melanoma cells associated with an increase of intracellular ROS, activation of caspase 3 and DNA fragmentation, suggesting that NPr-4-S-CAP mediated ROS production, eliciting apoptosis of melanoma cells. Growth of transplanted B16F1 melanomas was inhibited after the consecutive intratumoral injections of NPr-4-S-CAP, and the tumor growth after rechallenge of B16F1 was significantly suppressed in the treated mice. This suppression occurred when the treated mice were given the anti-CD4 antibody, but not the anti-CD8 antibody. Tetramer assay demonstrated increased TYRP-2-specific CD8 + T cells in the lymph node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice. Conclusions: These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells through ROS production and generates CD8 + cell immunity resulting in the suppression of rechallenged B16F1 melanoma.

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