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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1496346
Anti-colorectal cancer effect of total minor ginsenosides produced by lactobacilli transformation of major ginsenosides through inducing apoptosis and regulating gut microbiota
Provisionally accepted- 1 Jilin Academy of Agricultural Sciences (CAAS), Changchun, China
- 2 Tianjin University of Traditional Chinese Medicine, Tianjin, China
Objective: Minor ginsenosides have demonstrated promising anticancer effects in previous reports. Total minor ginsenosides (TMG) were obtained by fermentation of major ginsenosides with Lactiplantibacillus plantarum and potential anticancer effects of TMG on mouse colon cancer cell line CT26.WT in vitro and in vivo were investigated. Materials and Methods: We employed Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and western blot analysis in vitro to explore the anti-proliferative and pro-apoptotic functions of TMG in CT26. WT cells. In vivo, xenograft model was established by subcutaneously injecting mice with CT26. WT cells. and a dose of 100 mg/kg/day TMG to the tumor bearing mice. The level of apoptosis and expression of various proteins in the tumor tissues were detected by immunohistochemistry and western blot. High-throughput 16S rRNA sequencing was used to determine the alterations in the gut microbiota. Results: In vitro studies demonstrated that TMG significantly inhibited the proliferation and promoted apoptosis of CT26.WT cells. Interestingly, TMG induced apoptosis in CT26.WT cells through affecting the Bax/Bcl-2/caspase-3 pathway. Furthermore, the result of the transplanted tumor model indicated that TMG substantially enhanced the activity of Bax and caspase-3, reduced the activity of Bcl-2 and suppressed the expression of Raf/MEK/ERK protein levels. Fecal analysis revealed that TMG reconstructed the gut microbiota in colorectal cancer affected mice by augmenting the abundance of the advantageous bacterium Lactobacillus and 3 diminishing the abundance of the harmful bacterium Proteus.Conclusions: TMG can exhibit potent anti-colorectal cancer effects through diverse apoptotic mechanisms, and its mode of action was found to be closely related to the regulation of gut microbiota.
Keywords: ginsenoside, Lactic acid bacteria, minor ginsenosides, Apoptosis, anti-cancer, Gut Microbiota
Received: 14 Sep 2024; Accepted: 13 Dec 2024.
Copyright: © 2024 Shen, Gao, Yang, Zhao, Zhao, Gao and Li. 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:
Shengyu Li, Jilin Academy of Agricultural Sciences (CAAS), Changchun, China
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