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
. 2024 Aug;38(4):758-766.
doi: 10.1111/fcp.13000. Epub 2024 Mar 14.

Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple-negative breast cancer cells

Kunnathully Sudhan Sijisha  1 , Rajitha Anusha  1   2 , Sulochana Priya  1   2
Affiliations

Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple-negative breast cancer cells

Kunnathully Sudhan Sijisha et al. Fundam Clin Pharmacol. 2024 Aug.

Abstract

Background: Triple-negative breast cancer (TNBC) is the most aggressive and chemo-resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC.

Objective: This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells.

Methods: We examined the effects of EAD and paclitaxel alone and in combination in MDA-MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti-migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF-κB translocation.

Results: The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC50 concentrations, showed a synergistic effect in MDA-MB-231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel.

Conclusion: To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen.

Keywords: chemosensitization; epoxyazadiradione; paclitaxel; triple‐negative breast cancer.

PubMed Disclaimer

References

REFERENCES

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249. doi:10.3322/caac.21660
    1. Arnold M, Morgan E, Rumgay H, et al. Current and future burden of breast cancer: global statistics for 2020 and 2040. Breast. 2022;66:15‐23. doi:10.1016/j.breast.2022.08.010
    1. Chacón RD, Costanzo MV. Triple‐negative breast cancer. Breast Cancer Res. 2010;12(Suppl 2):S3. doi:10.1186/bcr2574
    1. He Y, Jiang Z, Chen C, Wang X. Classification of triple‐negative breast cancers based on immunogenomic profiling. J Exp Clin Cancer Res. 2018;37(1):327. doi:10.1186/s13046‐018‐1002‐1
    1. Nygren P. What is cancer chemotherapy? Acta Oncol. 2001;40(2–3):166‐174. doi:10.1080/02841860151116204

Grants and funding

LinkOut - more resources