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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| 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!
|
| _version_ | 1849226443365548032 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Keisuke Sano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae037a2480cb4a7386f49dcfc9ae7119 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ae037a2480cb4a7386f49dcfc9ae71192025-08-24T11:17:45ZengNature PortfolioScientific Reports2045-23222025-08-0115111010.1038/s41598-025-16225-9A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesisKeisuke Sano0Masanobu Shiga1Farhana Ferdousi2Hiromichi Sakurai3Kazuki Hamada4Kozaburo Tanuma5Satoshi Nitta6Yoshiyuki Nagumo7Shuya Kandori8Akio Hoshi9Hiromitsu Negoro10Bryan J. Mathis11Jun Miyazaki12Tran Ngoc Linh13Takashi Arimura14Hiroko Isoda15Hiroyuki Nishiyama16Department of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaInstitute of Life and Environmental Sciences, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Cardiovascular Surgery, University of TsukubaDepartment of Urology, School of Medicine, International University of Health and WelfareNational Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of TsukubaNational Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of TsukubaInstitute of Life and Environmental Sciences, University of TsukubaDepartment of Urology, Institute of Medicine, University of TsukubaAbstract 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.https://doi.org/10.1038/s41598-025-16225-9SqualeneEthylene glycol derivativeBladder cancerApoptosisSQLECholesterol metabolism |
| spellingShingle | 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 A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis Scientific Reports Squalene Ethylene glycol derivative Bladder cancer Apoptosis SQLE Cholesterol metabolism |
| title | A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis |
| title_full | A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis |
| title_fullStr | A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis |
| title_full_unstemmed | A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis |
| title_short | A novel, synthesized, amphiphilic ethylene glycol squalene derivative suppresses BBN-induced bladder carcinogenesis |
| title_sort | novel synthesized amphiphilic ethylene glycol squalene derivative suppresses bbn induced bladder carcinogenesis |
| topic | Squalene Ethylene glycol derivative Bladder cancer Apoptosis SQLE Cholesterol metabolism |
| url | https://doi.org/10.1038/s41598-025-16225-9 |
| work_keys_str_mv | AT keisukesano anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT masanobushiga anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT farhanaferdousi anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiromichisakurai anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT kazukihamada anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT kozaburotanuma anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT satoshinitta anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT yoshiyukinagumo anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT shuyakandori anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT akiohoshi anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiromitsunegoro anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT bryanjmathis anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT junmiyazaki anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT tranngoclinh anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT takashiarimura anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hirokoisoda anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiroyukinishiyama anovelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT keisukesano novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT masanobushiga novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT farhanaferdousi novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiromichisakurai novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT kazukihamada novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT kozaburotanuma novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT satoshinitta novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT yoshiyukinagumo novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT shuyakandori novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT akiohoshi novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiromitsunegoro novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT bryanjmathis novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT junmiyazaki novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT tranngoclinh novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT takashiarimura novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hirokoisoda novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis AT hiroyukinishiyama novelsynthesizedamphiphilicethyleneglycolsqualenederivativesuppressesbbninducedbladdercarcinogenesis |