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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1627656

Cepharanthine Hydrochloride Inhibits Prostate Cancer Progression by Modulating Gut Microbiota and Metabolites

Provisionally accepted
Hui  LiHui Li1Xing  LuoXing Luo2Peng  HePeng He1*Zongming  DongZongming Dong2Yongming  JiaYongming Jia2Bishao  SunBishao Sun2Ji  ZhengJi Zheng2*Jingzhen  ZhuJingzhen Zhu2*
  • 1Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China
  • 2Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

Background: Cepharanthine Hydrochloride (CH) is widely used in clinical settings to alleviate leukopenia caused by various tumors following radiotherapy and chemotherapy. However, it remains unclear whether CH have an inhibitory effect on the progression of prostate cancer, and whether this effect is mediated by gut microbiota. To address this question, the present study constructed normal mouse models of prostate cancer, as well as antibiotic-treated mouse models of prostate cancer.Methods: CH were then administered via gavage to both groups of model mice. After treatment, the tumor sizes of the mice were measured, and feces, blood, and tumor tissues from both groups were collected for 16S rDNA, metabolomics, and transcriptomics sequencing analysis. Results: Results showed CH treatment significantly suppressed prostate cancer growth in mice without antibiotic cocktail pretreatment, but not in antibiotic-pretreated mice. 16S rRNA sequencing revealed distinct gut microbiota alterations in CH-Ctrl versus Ctrl/CH-ABX groups, with increased g_Blautia, g_Lactobacillus, g_Butyricicoccus and decreased g_Akkermansia abundances. Metabolomic analysis identified 240 and 123 differentially abundant metabolites in CH-Ctrl vs. Ctrl and CH-ABX, respectively. RNA-seq detected 579 and 530 differentially expressed genes in CH-Ctrl vs. Ctrl and CH-ABX, respectively. Correlation analysis of differential gut microbiota, metabolites, and genes suggested that CH might inhibit prostate cancer growth by increasing the relative abundance of g_Blautia, g_Lactobacillus, and g_Butyricicoccus, suppressing g_Akkermansia proliferation, enhancing Acetylglycine metabolite production, upregulating Ttpa, Gm14964, Shc3, Elovl4 gene expression, and downregulating Gm10531, Bc021767 gene expression. Conclusion: This study is the first to explore the potential mechanisms of gut microbiota-mediated CH treatment for prostate cancer, providing a scientific basis for the application of CH in PCa therapy.

Keywords: prostate cancer, Cepharanthine hydrochloride, Gut Microbiota, metabolites of gut microbiota, antibiotic cocktail

Received: 20 May 2025; Accepted: 21 Jul 2025.

Copyright: © 2025 Li, Luo, He, Dong, Jia, Sun, Zheng and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Peng He, Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Ji Zheng, Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
Jingzhen Zhu, Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China

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