Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of vinorelbine in lung adenocarcinoma cells

Wei-Hsin Chiu, Helen H.W Chen, Jang-Yang Chang, Sheng Jie Luo, Chia Ling Li, Chia Ling Chen, Wu-Chou Su, Chiou Feng Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The standard treatment regimen for patients diagnosed with non-small cell lung cancer (NSCLC) with locally advanced stage III disease is concurrent chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated with radiation alone. Human lung adenocarcinoma cells were used in this study to investigate the molecular effects of glucosylceramide synthase inhibition on VNR-based CCRT. There was response rate of 66.7% with CCRT, which was better than the response rate observed with radiation alone (30.8%; P<0.001). CCRT caused an increase in cell cycle arrest at G2/M phase accompanied by apoptosis. Oxidative c-Jun N-terminal kinase (JNK) activation was involved in the increased apoptosis levels but not the cell cycle arrest. CCRT also induced an increase in ceramide accompanied by a decrease in glucosylceramide that was positively correlated with the cytotoxic effects. Pharmacologically inhibiting glucosylceramide synthase facilitated VNR- and CCRT-induced apoptosis by promoting the JNK pathway. Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of VNR by promoting JNK-mediated apoptosis in lung adenocarcinoma cells.

Original languageEnglish
Pages (from-to)144-151
Number of pages8
JournalCancer Letters
Volume349
Issue number2
DOIs
Publication statusPublished - 2014 Jul 28

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ceramide glucosyltransferase
Radiation-Sensitizing Agents
Chemoradiotherapy
JNK Mitogen-Activated Protein Kinases
Apoptosis
Cell Cycle Checkpoints
Non-Small Cell Lung Carcinoma
Radiation
Vinca Alkaloids
Glucosylceramides
Adenocarcinoma of lung
vinorelbine
Ceramides
G2 Phase
Cell Division

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of vinorelbine in lung adenocarcinoma cells",
abstract = "The standard treatment regimen for patients diagnosed with non-small cell lung cancer (NSCLC) with locally advanced stage III disease is concurrent chemoradiotherapy (CCRT). This study investigated the molecular effects of vinca alkaloid vinorelbine (VNR)-based CCRT. We reviewed the records of 68 patients with stage III NSCLC: 42 patients received VNR-based CCRT, and 26 were treated with radiation alone. Human lung adenocarcinoma cells were used in this study to investigate the molecular effects of glucosylceramide synthase inhibition on VNR-based CCRT. There was response rate of 66.7{\%} with CCRT, which was better than the response rate observed with radiation alone (30.8{\%}; P<0.001). CCRT caused an increase in cell cycle arrest at G2/M phase accompanied by apoptosis. Oxidative c-Jun N-terminal kinase (JNK) activation was involved in the increased apoptosis levels but not the cell cycle arrest. CCRT also induced an increase in ceramide accompanied by a decrease in glucosylceramide that was positively correlated with the cytotoxic effects. Pharmacologically inhibiting glucosylceramide synthase facilitated VNR- and CCRT-induced apoptosis by promoting the JNK pathway. Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of VNR by promoting JNK-mediated apoptosis in lung adenocarcinoma cells.",
author = "Wei-Hsin Chiu and Chen, {Helen H.W} and Jang-Yang Chang and Luo, {Sheng Jie} and Li, {Chia Ling} and Chen, {Chia Ling} and Wu-Chou Su and Lin, {Chiou Feng}",
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Inhibiting glucosylceramide synthase facilitates the radiosensitizing effects of vinorelbine in lung adenocarcinoma cells. / Chiu, Wei-Hsin; Chen, Helen H.W; Chang, Jang-Yang; Luo, Sheng Jie; Li, Chia Ling; Chen, Chia Ling; Su, Wu-Chou; Lin, Chiou Feng.

In: Cancer Letters, Vol. 349, No. 2, 28.07.2014, p. 144-151.

Research output: Contribution to journalArticle

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AU - Chiu, Wei-Hsin

AU - Chen, Helen H.W

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AU - Li, Chia Ling

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AU - Su, Wu-Chou

AU - Lin, Chiou Feng

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