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<p>The proliferative capacity and drug resistance of cancer cells are thought to be related to adaptations to the low nutrient and hypoxic conditions known as the tumor microenvironment. This adaptation is suggested to involve the unfolded protein response (UPR) triggered by the endoplasmic reticulum (ER) stress. Therefore, the ER stress induced under these conditions is considered one of the attractive targets for antitumor drug development. In this study, we designed and synthesized decenoic acid derivatives and found two compounds, 13-Chloro-6-(4-fluorophenoxy)tridec-6-en-8-yn-1-ol (<b>Cpd6</b>) and 13-Chloro-6-(4-methoxyphenoxy)tridec-6-en-8-yn-1-ol (<b>Cpd2</b>) showed cytotoxicity against human glioma cell-line, T98G, under the serum- and glucose-deprived condition. These two compounds exerted inhibitory effects on several ER and Golgi stress responses triggered under this low-nutrient condition. Furthermore, <b>Cpd6</b> profoundly downregulated the expression of c-Myc protein, a well-known oncogenic factor, in T98G cells. This study is expected to contribute to the development of fatty acid-derived antitumor compounds targeting the ER and Golgi stress responses.</p>

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Characterization of Novel Decenoic Acid Derivatives Exhibiting Cytotoxic Activity Against T98G Glioma Cells Under a Serum- and Glucose-deprived Condition

  • 期刊论文

  • 发表日期：

    2026年2月3日

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  • Yuma Ito,
  • Norihiro Tada,
  • Chihiro Muraki,
  • Yuta Kubota,
  • Mahmoud Kandeel,
  • Yukio Kitade,
  • Akichika Itoh,
  • Kentaro Oh-hashi

摘要

The proliferative capacity and drug resistance of cancer cells are thought to be related to adaptations to the low nutrient and hypoxic conditions known as the tumor microenvironment. This adaptation is suggested to involve the unfolded protein response (UPR) triggered by the endoplasmic reticulum (ER) stress. Therefore, the ER stress induced under these conditions is considered one of the attractive targets for antitumor drug development. In this study, we designed and synthesized decenoic acid derivatives and found two compounds, 13-Chloro-6-(4-fluorophenoxy)tridec-6-en-8-yn-1-ol (Cpd6) and 13-Chloro-6-(4-methoxyphenoxy)tridec-6-en-8-yn-1-ol (Cpd2) showed cytotoxicity against human glioma cell-line, T98G, under the serum- and glucose-deprived condition. These two compounds exerted inhibitory effects on several ER and Golgi stress responses triggered under this low-nutrient condition. Furthermore, Cpd6 profoundly downregulated the expression of c-Myc protein, a well-known oncogenic factor, in T98G cells. This study is expected to contribute to the development of fatty acid-derived antitumor compounds targeting the ER and Golgi stress responses.