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Cited by 102Phytochemistry and Bioactive CompoundsNatural product bioactivities and synthesisPhytochemical Studies and Bioactivities

Bufalin for an innovative therapeutic approach against cancer

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Soumoy, Laura, Ghanem, Ghanem E., Saussez, Sven, Journe, Fabrice·2022·Pharmacological Research
DOI 10.1016/j.phrs.2022.106442
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Abstract

Bufalin is an endogenous cardiotonic steroid, first discovered in toad venom but also found in the plasma of healthy humans, with anti-tumour activities in different cancer types. The current review is focused on its mechanisms of action and highlights its very large spectrum of effects both in vitro and in vivo. All leads to the conclusion that bufalin mediates its effects by affecting all the hallmarks of cancer and seems restricted to cancer cells avoiding side effects. Bufalin decreases cancer cell proliferation by acting on the cell cycle and inducing different mechanisms of cell death including apoptosis, necroptosis, autophagy and senescence. Bufalin also moderates metastasis formation by blocking migration and invasion as well as angiogenesis and by inducing a phenotype switch towards differentiation and decreasing cancer cell stemness. Regarding its various mechanisms of action in cancer cells, bufalin blocks overactivated signalling pathways and modifies cell metabolism. Moreover, bufalin gained lately a huge interest in the field of drug resistance by both reversing various drug resistance mechanisms and affecting the immune microenvironment. Together, these data support bufalin as a quite promising new anti-cancer drug candidate.

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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 [5]

    Section 7 reports inhibition of mTOR and SRC-3, including SRC-3’s target MIF as discussed in section 16.1, but says bufalin activates JNK and can either decrease or increase MAPK activity depending on the cancer type. Sections 2–4 describe apoptosis, necroptosis and autophagy; the review calls the second process necroptosis rather than necrosis. Searches for Hippo-YAP and Wnt/β-catenin did not establish suppression of those pathways in our copy, so the full list and its stated link to cell death are not supported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways.

    “Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways5,44–48.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [5]

    Sections 2–5 report bufalin-induced apoptosis, RIP1/ROS-dependent necroptosis, autophagy associated with p62 and AMPK, and p53-related senescence; page numbers are unavailable in our copy. The copy does not substantiate the claim that bufalin induces ferroptosis through DECR1 (searched: “ferroptosis” and “DECR1”). If the pathways are intended to correspond to the effects in the order listed, the copy links AMPK to autophagy, not apoptosis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Bufalin has emerged as a clinically validated natural compound with therapeutic potential across multiple cancer types.

    “Bufalin has emerged as a clinically validated natural compound with therapeutic potential across multiple cancer types.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [5]

    The Conclusions discuss bufalin’s antitumor effects across many cancer types and its potential to improve treatment. But §1.1, “Clinical trials on HuaChansu,” states that purified bufalin has never been administered to humans; the trials discussed tested HuaChansu, an extract containing bufalin. The claim’s “clinically validated” qualifier is therefore not supported for bufalin itself. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • Mechanistic studies reveal Bufalin's pleiotropic anti-tumor effects through cancer-type-specific targets.

    “Mechanistic studies reveal its pleiotropic anti-tumor effects through cancer-type-specific targets5,37.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [5]

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Cited by

Sorted by citations

Authors
Soumoy, L., Ghanem, G. E., Saussez, S., & Journe, F.
Affiliations
  • University of Mons (BE)
  • Université Libre de Bruxelles (BE)
Corresponding author
Soumoy, Laura
ORCID
Venue
Pharmacological Research
Publisher
Elsevier BV
Published
2022-10
Volume
184
Pages
106442
ISSN
1043-6618 (ISSN-L)
DOI
10.1016/j.phrs.2022.106442
OpenAlex
W4295517915
Cited by
102
References
2
Citations by year
2026: 18 · 2025: 34 · 2024: 33 · 2023: 16 · 2022: 1
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmacological Research (publishedVersion)
  • PubMed (publishedVersion)
  • ORBi UMONS (submittedVersion, other-oa)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Phytochemistry and Bioactive Compounds
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
Keywords
bufalin, cardiac glycosides, toad venom, antitumour activity, tumor cell proliferation, cell cycle arrest, apoptosis, necroptosis, autophagy, cellular senescence, metastasis, cell migration and invasion, angiogenesis, cancer stemness, cell differentiation, drug resistance reversal, tumor immune microenvironment, cellular metabolism, signaling pathways, cancer hallmarks
MeSH terms
Amphibian Venoms, Antineoplastic Agents, Bufanolides, Cardiac Glycosides, Humans, Neoplasms, Cell Line, Tumor, Cell Proliferation, Tumor Microenvironment

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