Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production
Abstract Colorectal cancer (CRC) is both a leading cause of cancer-related mortality and one of the most frequently diagnosed cancers. Previous studies have shown that zearalenone and theabrownin each exert anti-CRC effects. Here, we aimed to evaluate the anti-tumor properties of theabrownin and zea...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11820-2 |
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| author | Hoi Kit Matthew Leung Emily Kwun Kwan Lo Congjia Chen Fangfei Zhang Felicianna Marsena Jasiel Ismaiah Hani El-Nezami |
| author_facet | Hoi Kit Matthew Leung Emily Kwun Kwan Lo Congjia Chen Fangfei Zhang Felicianna Marsena Jasiel Ismaiah Hani El-Nezami |
| author_sort | Hoi Kit Matthew Leung |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is both a leading cause of cancer-related mortality and one of the most frequently diagnosed cancers. Previous studies have shown that zearalenone and theabrownin each exert anti-CRC effects. Here, we aimed to evaluate the anti-tumor properties of theabrownin and zearalenone mixture (TZ) and to assess whether supplementing TZ with 5-FU, a commonly used chemotherapeutic drug, could further suppress CRC tumorigenesis. Our results revealed that TZ significantly attenuated AOM/DSS-induced colorectal tumorigenesis. TZ improved survival rate, reduced tumor count, preserved colon length, and mitigated colonic inflammation in AOM/DSS mice. In addition, the concentration of pro-inflammatory cytokines IL-6, TNF-α and IL-17 A/F and proliferative PI3K/AKT were significantly reduced. Metagenomic analyses revealed that TZ modulated the gut microbiota and mycobiota composition and increased the fecal acetate and propionate levels. Furthermore, the enrichment of the bacterial Desulfovibrionaceae bacterium LT0009, Helicobacter sp. MIT 03-1616 and fungal Xylariaceae sp. FL0594 was associated with the reduction of tumor multiplicity and pro-inflammatory cytokines. No additional benefits were observed with combining TZ with 5-FU. Taken together, TZ presented remarkable inhibitory effects on colorectal tumorigenesis, indicating its potential as a novel therapeutic candidate for CRC. |
| format | Article |
| id | doaj-art-f8d2644a30fc4054b292a17d92f7f74d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-f8d2644a30fc4054b292a17d92f7f74d2025-08-20T03:46:01ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-11820-2Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate productionHoi Kit Matthew Leung0Emily Kwun Kwan Lo1Congjia Chen2Fangfei Zhang3Felicianna4Marsena Jasiel Ismaiah5Hani El-Nezami6School of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongSchool of Biological Sciences, University of Hong KongAbstract Colorectal cancer (CRC) is both a leading cause of cancer-related mortality and one of the most frequently diagnosed cancers. Previous studies have shown that zearalenone and theabrownin each exert anti-CRC effects. Here, we aimed to evaluate the anti-tumor properties of theabrownin and zearalenone mixture (TZ) and to assess whether supplementing TZ with 5-FU, a commonly used chemotherapeutic drug, could further suppress CRC tumorigenesis. Our results revealed that TZ significantly attenuated AOM/DSS-induced colorectal tumorigenesis. TZ improved survival rate, reduced tumor count, preserved colon length, and mitigated colonic inflammation in AOM/DSS mice. In addition, the concentration of pro-inflammatory cytokines IL-6, TNF-α and IL-17 A/F and proliferative PI3K/AKT were significantly reduced. Metagenomic analyses revealed that TZ modulated the gut microbiota and mycobiota composition and increased the fecal acetate and propionate levels. Furthermore, the enrichment of the bacterial Desulfovibrionaceae bacterium LT0009, Helicobacter sp. MIT 03-1616 and fungal Xylariaceae sp. FL0594 was associated with the reduction of tumor multiplicity and pro-inflammatory cytokines. No additional benefits were observed with combining TZ with 5-FU. Taken together, TZ presented remarkable inhibitory effects on colorectal tumorigenesis, indicating its potential as a novel therapeutic candidate for CRC.https://doi.org/10.1038/s41598-025-11820-2TZColorectal cancerGut microbiotaGut mycobiotaShort-chain fatty acids |
| spellingShingle | Hoi Kit Matthew Leung Emily Kwun Kwan Lo Congjia Chen Fangfei Zhang Felicianna Marsena Jasiel Ismaiah Hani El-Nezami Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production Scientific Reports TZ Colorectal cancer Gut microbiota Gut mycobiota Short-chain fatty acids |
| title | Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production |
| title_full | Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production |
| title_fullStr | Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production |
| title_full_unstemmed | Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production |
| title_short | Theabrownin combined with zearalenone suppresses colitis-associated colorectal cancer by inhibiting PI3K/AKT pathway and enhancing microbial propionate production |
| title_sort | theabrownin combined with zearalenone suppresses colitis associated colorectal cancer by inhibiting pi3k akt pathway and enhancing microbial propionate production |
| topic | TZ Colorectal cancer Gut microbiota Gut mycobiota Short-chain fatty acids |
| url | https://doi.org/10.1038/s41598-025-11820-2 |
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