Gamabufotalin Suppresses Colorectal Cancer Growth via Oxidative Stress-Induced Apoptosis and DNA Synthesis Inhibition
| Author | Hui Nie | en |
| Author | Anfang Cui | en |
| Author | Zhicheng Sun | en |
| Author | Zhaoyang Li | en |
| Author | Jianhua Guo | en |
| Author | Shuhao Fan | en |
| Author | Xiangchen Wang | en |
| Author | Yong Xia | en |
| Orcid | Jianhua Guo [0009-0000-7312-4205] | en |
| Orcid | Yong Xia [0000-0002-1020-0263] | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: Colorectal cancer (CRC) continues to be a major cause of cancer-related mortality worldwide, creating an urgent need to develop novel therapeutic agents that are both highly effective and minimally toxic. Gamabufotalin (GA), a bioactive bufadienolide compound, has shown promising antitumor potential, including against CRC; however, its precise mechanisms of action in CRC remain incompletely understood. Objectives: The aim of this study was to investigate the therapeutic effect of GA on CRC and explore the underlying molecular mechanisms. Methods: A combination of in vitro and in vivo approaches was employed, including cell viability assays, colony formation, EdU incorporation, cell cycle and apoptosis analyses by flow cytometry, ROS and mitochondrial membrane potential detection, as well as integrated transcriptomic and proteomic profiling. The in vivo antitumor efficacy was further validated in a nude mouse xenograft model. Results: Gamabufotalin exhibited potent, dose-dependent anti-CRC activity in vitro (IC50: 24-30 nM) with high selectivity over normal cells. It triggered mitochondrial apoptosis via ROS generation and arrested the cell cycle, suppressing DNA synthesis. Integrated omics revealed TP53I3/PIG3 upregulation and RFC3/NUCKS1 downregulation as key mechanisms. Critically, these effects converged to suppress tumor growth in vivo without systemic toxicity. Conclusions: Gamabufotalin selectively and potently inhibits CRC through dual mechanisms: Inducing ROS-mediated apoptosis and suppressing proliferation. With a favorable therapeutic index and defined molecular targets, GA represents a promising candidate for CRC therapy. | en |
| DOI | https://doi.org/10.5812/ijpr-169859 | en |
| URI | https://brieflands.com/journals/ijpr/articles/169859 | en |
| Keyword | Gamabufotalin | en |
| Keyword | Colorectal Cancer | en |
| Keyword | Oxidative Stress | en |
| Keyword | Apoptosis | en |
| Keyword | DNA Synthesis | en |
| Publisher | Brieflands | en |
| Title | Gamabufotalin Suppresses Colorectal Cancer Growth via Oxidative Stress-Induced Apoptosis and DNA Synthesis Inhibition | en |
| Type | Research Article | en |