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Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs

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Farooqi, Ammad Ahmad, Rakhmetova, Venera S., Kapanova, Gulnara, Tashenova, Gulnara, Tulebayeva, Aigul, Akhenbekova, Aida, Ibekenov, Onlassyn, Turgambayeva, Assiya +1 more·2023·Molecules
DOI 10.3390/molecules28052231PMC PMC10004807
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Abstract

The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

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  • Bufalin could suppress multiple signaling pathways, including Hippo-YAP, Wnt/β-Catenin, JNK, SRC3/MIF, mTOR, and MAPK, leading to apoptosis, necrosis, and autophagy in different cancer cells.

    “Current pharmacological research suggests that Bufalin could suppress multiple signaling pathways, including Hippo-YAP, Wnt/β-Catenin, JNK, SRC3/MIF, mTOR, and MAPK, leading to apoptosis, necrosis, and autophagy in different cancer cells3,5–8.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [3]

    Section 3 reports that bufalin inhibits AKT/mTOR signaling, with evidence of apoptosis and autophagy in cancer cells; section 4 reports reduced β-catenin signaling. The copy does not substantiate suppression of Hippo-YAP or SRC3/MIF, or bufalin-induced necrosis. Section 5 instead describes enhanced JNK and p38 MAPK activation with bufalin and TRAIL, not their suppression. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Bufalin exerts effective anti-tumor action against lung cancer, liver cancer, colorectal cancer, and glioma.

    “Accumulating evidence indicates that Bufalin exerts effective anti-tumor action against lung cancer, liver cancer, colorectal cancer, and glioma3,4.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [3]

  • Bufalin has been reported to inhibit key signaling pathways such as mTOR, Wnt/β-catenin, and Akt, which are necessary for cancer cell survival, proliferation, and migration.

    “Bufalin has been reported to inhibit key signaling pathways such as mTOR, Wnt/β-catenin, and Akt, which are necessary for cancer cell survival, proliferation, and migration3.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [3]

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Cited by

Sorted by citations

Authors
Farooqi, A. A., Rakhmetova, V. S., Kapanova, G., Tashenova, G., Tulebayeva, A., Akhenbekova, A., Ibekenov, O., Turgambayeva, A., & Xu, B.
Affiliations
  • Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan
  • Astana Medical University (KZ)
  • Al-Farabi Kazakh National University (KZ)
  • Kazakh National Medical University (KZ)
  • Beijing Normal-Hong Kong Baptist University (CN)
Corresponding author
Xu, Baojun
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2023-02-27
Volume
28
Issue
5
Pages
2231
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules28052231
PMC
PMC10004807
OpenAlex
W4322620044
Cited by
25
References
2
Citations by year
2026: 5 · 2025: 5 · 2024: 11 · 2023: 4
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
BNU-HKBU United International College (UICR202107)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
Keywords
bufalin, Bufo gargarizans, Bufo melanostictus, natural products, chemoprevention, JAK/STAT signaling, Wnt/β-catenin signaling, mTOR signaling, TRAIL, TRAIL receptors, EGFR, c-Met, non-coding RNA, tumor microenvironment, tumor-associated macrophages, metastasis, carcinogenesis, multi-target therapy
MeSH terms
Animals, Bufanolides, Signal Transduction, Apoptosis, Cell Line, Tumor, beta Catenin, TOR Serine-Threonine Kinases, Tumor Microenvironment, Carcinogenesis

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