Journal Article

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

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

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/45 / 631/67 / 692/4025 / 692/4028 / 692/699 / Animals / Apoptosis / Apoptosis - drug effects / Biosynthesis / Bladder cancer / Butylhydroxybutylnitrosamine - toxicity / Cancer therapies / Carcinogenesis / Carcinogenesis - chemically induced / Carcinogenesis - drug effects / Cell Line, Tumor / Cell Proliferation - drug effects / Cholesterol / Cholesterol - biosynthesis / Cholesterol metabolism / Diethylene glycol / DNA damage / DNA Damage - drug effects / Ethylene glycol / Ethylene Glycol - chemistry / Ethylene glycol derivative / Experiments / Female / Females / Genes / Humanities and Social Sciences / Humans / Immunostimulation / Invoices / Mice / Mice, Inbred C57BL / Microenvironments / multidisciplinary / Nitrosamines / Oral administration / Oxidative stress / Permeability / Science / Science (multidisciplinary) / SQLE / Squalene / Squalene - analogs & derivatives / Squalene - chemical synthesis / Squalene - chemistry / Squalene - pharmacology / Standard deviation / Transcriptomics / Tumor cell lines / Tumorigenesis / Urinary Bladder Neoplasms - chemically induced / Urinary Bladder Neoplasms - drug therapy / Urinary Bladder Neoplasms - metabolism / Urinary Bladder Neoplasms - pathology