Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Oct 4:14:1274336.
doi: 10.3389/fphar.2023.1274336. eCollection 2023.

An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

Qingmei Ye #  1   2 , Xin Zhou #  3 , Han Ren #  1 , Fangxuan Han  1 , Rong Lin  4 , Juan Li  4
Affiliations
Review

An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

Qingmei Ye et al. Front Pharmacol. .

Abstract

Profound progress has been made in cancer treatment in the past three decades. However, drug resistance remains prevalent and a critical challenge. Drug resistance can be attributed to oncogenes mutations, activated defensive mechanisms, ATP-bind cassette transporters overexpression, cancer stem cells, etc. Chinese traditional medicine toad venom has been used for centuries for different diseases, including resistant cancers. Bufalin is one of the bufadienolides in toad venom that has been extensively studied for its potential in refractory and drug-resistant cancer treatments in vitro and in vivo. In this work, we would like to critically review the progress made in the past decade (2013-2022) of bufalin in overcoming drug resistance in cancers. Generally, bufalin shows high potential in killing certain refractory and resistant cancer cells via multiple mechanisms. More importantly, bufalin can work as a chemo-sensitizer that enhances the sensitivity of certain conventional and targeted therapies at low concentrations. In addition, the development of bufalin derivatives was also briefly summarized and discussed. We also analyzed the obstacles and challenges and provided possible solutions for future perspectives. We hope that the collective information may help evoke more effort for more in-depth studies and evaluation of bufalin in both lab and possible clinical trials.

Keywords: bufalin; drug resistance; mechanisms; overcome; refractory cancers.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Multifaceted mechanisms contribute to drug resistance in cancers.
FIGURE 2
FIGURE 2
Structures of Bufalin and its derivatives. The primary structural differences in different rings are highlighted.
FIGURE 3
FIGURE 3
Bufalin has shown potential in treating refractory cancers by regulating various targets.
FIGURE 4
FIGURE 4
Bufalin has shown potential in working as a chemo-sensitizer.
FIGURE 5
FIGURE 5
(A) Structures of several prominent bufalin derivatives. Significant structural properties are highlighted. (B) SAR information of bufalin by far (as of February 2023), and some remaining open questions to be answered.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Aravindan N., Jain D., Somasundaram D. B., Herman T. S., Aravindan S. (2019). Cancer stem cells in neuroblastoma therapy resistance. Cancer Drug Resist 2, 948–967. 10.20517/cdr.2019.72 - DOI - PMC - PubMed
    1. Ashrafi A., Akter Z., Modareszadeh P., Modareszadeh P., Berisha E., Alemi P. S., et al. (2022). Current landscape of therapeutic resistance in lung cancer and promising strategies to overcome resistance. Cancers 14, 4562. 10.3390/cancers14194562 - DOI - PMC - PubMed
    1. Beebe J., Josephraj S., Wang C. J., Danielson J., Cui Q., Huang C., et al. (2022). Therapeutic activity of the lansoprazole metabolite 5-hydroxy lansoprazole sulfide in triple-negative breast cancer by inhibiting the enoyl reductase of fatty acid synthase. J. Med. Chem. 65, 13681–13691. 10.1021/acs.jmedchem.2c00642 - DOI - PubMed
    1. Bengtsson A., Andersson R., Ansari D. (2020). The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. Sci. Rep-Uk 10, 16425. 10.1038/s41598-020-73525-y - DOI - PMC - PubMed
    1. Bielack S. S., Blattmann C., Borkhardt A., Csóka M., Hassenpflug W., Kabíčková E., et al. (2022), Osteosarcoma and causes of death: A report of 1520 deceased patients from the cooperative osteosarcoma study group (COSS). Eur. J. Cancer 176, 50–57. 10.1016/j.ejca.2022.09.007 - DOI - PubMed