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

详细信息	查看全文 | 推荐本文 |

• 作者：Yasue Ishii-Osai<sup>asup> ; Toshiharu Yamashita<sup>asup><sup> ; sup><sup>yamasita@sapmed.ac.jpsup> ; Yasuaki Tamura<sup>bsup> ; Noriyuki Sato<sup>bsup> ; Akira Ito<sup>csup> ; Hiroyuki Honda<sup>dsup> ; Kazumasa Wakamatsu<sup>esup> ; Shosuke Ito<sup>esup> ; Eiichi Nakayama<sup>fsup> ; Masae Okura<sup>asup> ; Kowichi Jimbow<sup>asup>
• 关键词：NPr-4-S-CAP ; N-propionyl-4-S-cysteaminylphenol ; NPr-2-S-CAP ; N-propionyl-2-S-cysteaminylphenol ; AMF ; alternating magnetic field ; ROS ; reactive oxygen species ; TRAIL ; tumor necrosis factor-related apoptosis-inducing ligand ; DMEM ; Dulbecco's modified Eagle'
• 刊名：Journal of Dermatological Science
• 出版年：2012
• 期刊代码：153_09231811
• 类别：med
• 出版时间：July, 2012
• 卷：67
• 期：1
• 页码：51-60
• 文件大小：2020 K

摘要

ss="h4">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.

ss="h4">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.

ss="h4">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.

ss="h4">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<sup>+sup> T cells in the lymph node and spleen cells prepared from NPr-4-S-CAP-treated B16F1-bearing mice.

ss="h4">Conclusions

These suggest that NPr-4-S-CAP induces apoptosis in melanoma cells through ROS production and generates CD8<sup>+sup> cell immunity resulting in the suppression of rechallenged B16F1 melanoma.