Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation
Epidemiological evidence suggests that kava (<i>Piper methysticum Forst</i>) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms....
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/3/521 |
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| author | Xia Xu Xuejiao Tian Liankun Song Jun Xie Joseph C. Liao Joshua J. Meeks Xue-Ru Wu Greg E. Gin Beverly Wang Edward Uchio Xiaolin Zi |
| author_facet | Xia Xu Xuejiao Tian Liankun Song Jun Xie Joseph C. Liao Joshua J. Meeks Xue-Ru Wu Greg E. Gin Beverly Wang Edward Uchio Xiaolin Zi |
| author_sort | Xia Xu |
| collection | DOAJ |
| description | Epidemiological evidence suggests that kava (<i>Piper methysticum Forst</i>) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers. |
| first_indexed | 2024-03-11T06:52:56Z |
| format | Article |
| id | doaj.art-ca3d8acc98a94b708e72c263ca4a2738 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:52:56Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ca3d8acc98a94b708e72c263ca4a27382023-11-17T09:52:28ZengMDPI AGBiomolecules2218-273X2023-03-0113352110.3390/biom13030521Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 MethylationXia Xu0Xuejiao Tian1Liankun Song2Jun Xie3Joseph C. Liao4Joshua J. Meeks5Xue-Ru Wu6Greg E. Gin7Beverly Wang8Edward Uchio9Xiaolin Zi10Department of Urology, University of California, Irvine, Orange, CA 92868, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USAVeterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USAJesse Brown VA Medical Center, 820 S Damen Ave, Chicago, IL 60612, USAVeterans Affairs New York Harbor Healthcare System, New York, NY 10010, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USADepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA 92868, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USADepartment of Urology, University of California, Irvine, Orange, CA 92868, USAEpidemiological evidence suggests that kava (<i>Piper methysticum Forst</i>) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.https://www.mdpi.com/2218-273X/13/3/521kavaLSD1chemopreventionbladder cancer |
| spellingShingle | Xia Xu Xuejiao Tian Liankun Song Jun Xie Joseph C. Liao Joshua J. Meeks Xue-Ru Wu Greg E. Gin Beverly Wang Edward Uchio Xiaolin Zi Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation Biomolecules kava LSD1 chemoprevention bladder cancer |
| title | Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation |
| title_full | Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation |
| title_fullStr | Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation |
| title_full_unstemmed | Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation |
| title_short | Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation |
| title_sort | kawain inhibits urinary bladder carcinogenesis through epigenetic inhibition of lsd1 and upregulation of h3k4 methylation |
| topic | kava LSD1 chemoprevention bladder cancer |
| url | https://www.mdpi.com/2218-273X/13/3/521 |
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