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Updated: Aug 15, 2026
Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine
Published on: October 13, 2023
Bufothionine inhibits colorectal cancer progression via the STAT3/p53/SLC7A11 signaling axis
Ruifang Xie1, Nan Xiang1, Gui Zhou1
1Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background:
Bufothionine, a major bioactive component of dried toad skin, has shown anti-tumor potential. However, its efficacy and underlying mechanisms in colorectal cancer (CRC) remain unclear.
Objective:
This study aimed to investigate the therapeutic potential of bufothionine and its underlying mechanisms against CRC.
Methods:
Anti-tumor efficacy was assessed using in vitro (CCK-8, migration assays) and in vivo (HT-29 xenograft) models. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict targets. Mechanisms were validated by biochemical assays, Western blot, IHC, and qPCR, with ferrostatin-1 applied to confirm ferroptosis specificity.
Results:
Bufothionine significantly inhibited HT-29 cell proliferation and migration. Integrated network pharmacology and computational modeling identified p53 and STAT3 as core targets, with potential interactions predicted between bufothionine and key ferroptosis regulators (including SLC7A11). In vitro, bufothionine induced ferroptosis, characterized by increased Fe2+, ROS, and MDA levels, and a decreased GSH/GSSG ratio; these effects were partially reversed by ferrostatin-1. In vivo, bufothionine reduced tumor weight indices, improved liver function by attenuating AST and ALP elevations without hepatosplenic toxicity, and regulated inflammatory cytokines. Mechanistically, bufothionine suppressed inflammatory activation (NLRP3, IL-1β), inhibited STAT3 phosphorylation, and modulated p53 activity, leading to the subsequent inhibition of the SLC7A11/GPX4 axis in both cells and tumor tissues.
Conclusion:
Bufothionine suppresses CRC by the STAT3/p53/SLC7A11 signaling axis in a manner associated with ferroptosis, suggesting its potential as a therapeutic agent for colorectal cancer.
Insights
Bufothionine, derived from toad skin, shows anti-cancer effects in colorectal cancer (CRC) by inducing ferroptosis. It targets the STAT3/p53/SLC7A11 pathway, offering potential as a novel CRC therapeutic.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Bufothionine, a bioactive compound from dried toad skin, exhibits potential anti-tumor properties.
- Its specific efficacy and mechanisms against colorectal cancer (CRC) require elucidation.
Purpose of the Study:
- To investigate the therapeutic potential of bufothionine in colorectal cancer.
- To elucidate the underlying molecular mechanisms of bufothionine's anti-cancer effects in CRC.
Main Methods:
- Utilized in vitro (cell proliferation, migration) and in vivo (xenograft) models to assess anti-tumor efficacy.
- Employed network pharmacology, molecular docking, and simulations to predict therapeutic targets.
- Validated mechanisms via biochemical assays, Western blot, IHC, qPCR, and ferroptosis-specific inhibitors.
Main Results:
- Bufothionine significantly inhibited HT-29 cell proliferation and migration.
- Identified p53 and STAT3 as core targets, predicting interactions with ferroptosis regulators like SLC7A11.
- Demonstrated bufothionine-induced ferroptosis in vitro and in vivo, involving increased oxidative stress and modulated inflammatory pathways.
- Showed bufothionine suppressed tumor growth, improved liver function, and regulated inflammatory cytokines without toxicity.
- Mechanistically, bufothionine inhibited STAT3 phosphorylation and modulated p53 activity, downregulating the SLC7A11/GPX4 axis.
Conclusions:
- Bufothionine suppresses colorectal cancer through the STAT3/p53/SLC7A11 signaling axis.
- The anti-cancer effects are associated with the induction of ferroptosis.
- Bufothionine presents potential as a novel therapeutic agent for colorectal cancer.
