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Biomedical

Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism

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Zhongbo Liu,

Zhongbo Liu

Department of Urology, University of California Irvine, Orange, CA 92868, USA


Liankun Song,

Liankun Song

Department of Urology, University of California Irvine, Orange, CA 92868, USA


Jun Xie,

Jun Xie

Department of Urology, University of California Irvine, Orange, CA 92868, USA


Xue-Ru Wu,

Xue-Ru Wu

Department of Urology, NYU School of Medicine, New York, NY 10016, USA


Greg E. Gin,

Greg E. Gin

Department of Urology, University of California Irvine, Orange, CA 92868, USA


Beverly Wang,

Beverly Wang

Department of Pathology and Laboratory Medicine, University of California, Irvine, Orange, CA 92868, USA


Edward Uchio,

Edward Uchio

Department of Urology, University of California Irvine, Orange, CA 92868, USA


Xiaolin Zi

Xiaolin Zi

Department of Urology, University of California Irvine, Orange, CA 92868, USA


  Peer Reviewed

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© attribution CC-BY

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518 Views

Added on

2024-11-03

Doi: http://dx.doi.org/10.3390/molecules28041666

Related Subjects
Anatomy
Biochemistry
Epidemiology
Genetics
Neuroscience
Psychology
Oncology
Medicine
Musculoskeletal science
Pediatrics
Pathology
Pharmacology
Physiology
Psychiatry
Primary care
Women and reproductive health

Abstract

UPII-mutant Ha-ras transgenic mice develop urothelial hyperplasia and low-grade papillary carcinoma, which mimics human non-muscle invasive bladder cancer (NMIBC). We investigated the effects and mechanisms of kawain, a main kavalactone in the kava plant, on oncogenic Ha-ras-driven urothelial carcinoma in these mice. The mice were fed at six weeks of age with vehicle control or kawain (6 g/kg) formulated food for approximately five months. Seventy-eight percent of the mice or more fed with kawain food survived more than six months of age, whereas only 32% control food-fed male mice survived, (p = 0.0082). The mean wet bladder weights (a surrogate for tumor burden) of UPII-mutant Ha-ras transgenic mice with kawain diet was decreased by approximately 56% compared to those fed with the control diet (p = 0.035). The kawain diet also significantly reduced the occurrence of hydronephrosis and hematuria in UPII-mutant Ha-ras transgenic mice. Histological examination and immunohistochemistry analysis revealed that vehicle control-treated mice displayed more urothelial carcinoma and Ki67-positive cells in the bladder compared to kawain treated mice. Global metabolic profiling of bladder tumor samples from mice fed with kawain food showed significantly more enrichment of serotonin and less abundance of xylulose, prostaglandin A2, D2 and E2 compared to those from control diet-fed mice, suggesting decreased shunting of glucose to the pentose phosphate pathway (PPP) and reduced inflammation. In addition, kawain selectively inhibited the growth of human bladder cancer cell lines with a significant suppression of 4E-BP1 expression and rpS6 phosphorylation. These observations indicate a potential impact of kawain consumption on bladder cancer prevention by rewiring the metabolic programs of the tumor cells.

Key Questions about Kawain's Effect on Urothelial Tumorigenesis

The article "Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism" investigates the effects of kawain, a primary kavalactone in the kava plant, on urothelial carcinoma driven by oncogenic Ha-ras in mice. The study demonstrates that kawain administration leads to a significant reduction in tumor incidence and size. Mechanistically, kawain inhibits the mTOR signaling pathway and alters cancer metabolism, suggesting its potential as a therapeutic agent for bladder cancer.

1. What is the effect of kawain on urothelial carcinoma in UPII-mutant Ha-ras mice?

The study found that kawain administration significantly reduced both the incidence and size of tumors in UPII-mutant Ha-ras mice, indicating its potential as a therapeutic agent for bladder cancer.

2. How does kawain inhibit tumor growth?

Kawain inhibits tumor growth by suppressing the mTOR signaling pathway and altering cancer metabolism, which are crucial for tumor cell proliferation and survival.

3. What are the implications of these findings for bladder cancer therapy?

The findings suggest that kawain could be developed as a novel therapeutic approach for bladder cancer, offering a potential alternative to conventional treatments.

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Article usage: Nov-2024 to May-2025
Show by month Manuscript Video Summary
2025 May 118 118
2025 April 67 67
2025 March 72 72
2025 February 49 49
2025 January 85 85
2024 December 61 61
2024 November 66 66
Total 518 518
Show by month Manuscript Video Summary
2025 May 118 118
2025 April 67 67
2025 March 72 72
2025 February 49 49
2025 January 85 85
2024 December 61 61
2024 November 66 66
Total 518 518
Related Subjects
Anatomy
Biochemistry
Epidemiology
Genetics
Neuroscience
Psychology
Oncology
Medicine
Musculoskeletal science
Pediatrics
Pathology
Pharmacology
Physiology
Psychiatry
Primary care
Women and reproductive health
copyright icon

© attribution CC-BY

  • 0

rating
518 Views

Added on

2024-11-03

Doi: http://dx.doi.org/10.3390/molecules28041666

Related Subjects
Anatomy
Biochemistry
Epidemiology
Genetics
Neuroscience
Psychology
Oncology
Medicine
Musculoskeletal science
Pediatrics
Pathology
Pharmacology
Physiology
Psychiatry
Primary care
Women and reproductive health

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