Journal of ethnopharmacology · 2025
Mechanistic analysis of anti-prostate cancer and toxicity-reducing effects of bufadienolides extracts: Comparative efficacy and safety with isolated bioactive compounds.
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Lin Rong, Ye Qingmei, He Qi, Kim Dong-Seon, Chen Daihong, Jin Lu, Wang Wenguang, Li Juan
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Bufonis Venenum, a traditional ethnic drug, has shown potential efficacy in managing cancer, cardiovascular diseases, pain, and inflammation. Bufadienolides, its primary active constituents, exhibit potent antitumor activity.
AIM OF THE STUDY: This study investigates the anti-prostate cancer and toxicity-reducing properties of bufadienolides extracts.
MATERIALS AND METHODS: The bufadienolides compounds were characterized using LC-MS/MS. Prostate cancer cells, normal prostate cells, and H9c2 cells were treated with bufadienolides extracts and its main compounds. Cell proliferation and migration were evaluated using MTT and scratch assays, while apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry and the DCFH-DA fluorescence probe. Additionally, transcriptome-metabolomics analysis was employed to elucidate regulatory pathways, which were further verified by qRT-PCR and Western blot (WB). Bufadienolides' toxicity and antitumor effects were assessed using acute toxicity assays and an H22 tumor-bearing mouse model.
RESULTS: Apart from eight bufadienolides compounds, the formation of aggregates, such as dimers of monomeric compounds, was identified within the extracts. Bufadienolides extracts and its major components, bufalin and resibufogenin, significantly inhibited prostate cancer cell proliferation and migration, induced apoptosis, and promoted ROS production. They modulated key biological processes, including IL-17, TNF, MAPK, and mTOR signaling, lipid metabolism, and pantothenate and CoA biosynthesis. Notably, extracts exhibited superior efficacy compared to bufalin and resibufogenin in both in vitro and in vivo experiments.
CONCLUSION: The combined action of multiple bufadienolides in the extract may enhance their overall efficacy and safety, highlighting their potential as therapeutic agent for prostate cancer.
AIM OF THE STUDY: This study investigates the anti-prostate cancer and toxicity-reducing properties of bufadienolides extracts.
MATERIALS AND METHODS: The bufadienolides compounds were characterized using LC-MS/MS. Prostate cancer cells, normal prostate cells, and H9c2 cells were treated with bufadienolides extracts and its main compounds. Cell proliferation and migration were evaluated using MTT and scratch assays, while apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry and the DCFH-DA fluorescence probe. Additionally, transcriptome-metabolomics analysis was employed to elucidate regulatory pathways, which were further verified by qRT-PCR and Western blot (WB). Bufadienolides' toxicity and antitumor effects were assessed using acute toxicity assays and an H22 tumor-bearing mouse model.
RESULTS: Apart from eight bufadienolides compounds, the formation of aggregates, such as dimers of monomeric compounds, was identified within the extracts. Bufadienolides extracts and its major components, bufalin and resibufogenin, significantly inhibited prostate cancer cell proliferation and migration, induced apoptosis, and promoted ROS production. They modulated key biological processes, including IL-17, TNF, MAPK, and mTOR signaling, lipid metabolism, and pantothenate and CoA biosynthesis. Notably, extracts exhibited superior efficacy compared to bufalin and resibufogenin in both in vitro and in vivo experiments.
CONCLUSION: The combined action of multiple bufadienolides in the extract may enhance their overall efficacy and safety, highlighting their potential as therapeutic agent for prostate cancer.