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

Abstract 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 blad...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-16225-9
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
ISSN:2045-2322