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<p>Squalene, a natural triterpene with antioxidant, anti-inflammatory, and immunostimulatory properties, holds promise for cancer therapy. Here, we examined a previously developed, diethylene glycol derivative of squalene (SQ-diEG) and investigated its in vivo anti-carcinogenic effects in bladder cancer. C57BL/6 mice were treated with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to induce bladder cancer, with SQ-diEG or PBS (control) administered orally from Week 0. SQ-diEG significantly reduced bladder cancer incidence to 3.7% after 8&#xa0;weeks, compared to 21.4% in controls (p = 0.025). Transcriptomic analysis indicated that SQ-diEG may exert anti-carcinogenic effects by reducing ROS-mediated DNA damage, enhancing the immune microenvironment, and modulating cholesterol biosynthesis via SQLE downregulation. In vitro, SQ-diEG inhibited proliferation and induced apoptosis in bladder cancer cell lines. This study is the first to demonstrate that SQ-diEG significantly reduces bladder cancer in a BBN mouse model, highlighting potential for therapeutic development. Further research is needed to elucidate the mechanisms and long-term efficacy of SQ-diEG.</p>

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A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月21日

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  • Keisuke Sano,
  • Masanobu Shiga,
  • Farhana Ferdousi,
  • Hiromichi Sakurai,
  • Kazuki Hamada,
  • Kozaburo Tanuma,
  • Satoshi Nitta,
  • Yoshiyuki Nagumo,
  • Shuya Kandori,
  • Akio Hoshi,
  • Hiromitsu Negoro,
  • Bryan J. Mathis,
  • Jun Miyazaki,
  • Tran Ngoc Linh,
  • Takashi Arimura,
  • Hiroko Isoda,
  • Hiroyuki Nishiyama

摘要

Squalene, a natural triterpene with antioxidant, anti-inflammatory, and immunostimulatory properties, holds promise for cancer therapy. Here, we examined a previously developed, diethylene glycol derivative of squalene (SQ-diEG) and investigated its in vivo anti-carcinogenic effects in bladder cancer. C57BL/6 mice were treated with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to induce bladder cancer, with SQ-diEG or PBS (control) administered orally from Week 0. SQ-diEG significantly reduced bladder cancer incidence to 3.7% after 8 weeks, compared to 21.4% in controls (p = 0.025). Transcriptomic analysis indicated that SQ-diEG may exert anti-carcinogenic effects by reducing ROS-mediated DNA damage, enhancing the immune microenvironment, and modulating cholesterol biosynthesis via SQLE downregulation. In vitro, SQ-diEG inhibited proliferation and induced apoptosis in bladder cancer cell lines. This study is the first to demonstrate that SQ-diEG significantly reduces bladder cancer in a BBN mouse model, highlighting potential for therapeutic development. Further research is needed to elucidate the mechanisms and long-term efficacy of SQ-diEG.