TR
EN
Effect of doxorubicin on Caspase-1/GSDMD-mediated pyroptosis in MCF-7 breast cancer spheroids
Abstract
Aim: Doxorubicin, a widely used anthracycline antibiotic, exerts its antitumor effects through multiple mechanisms, including DNA intercalation, inhibition of topoisomerase II, and the induction of oxidative stress. This study aimed to evaluate its potential to activate the inflammatory cell death pathway, pyroptosis via Caspase-1 and Gasdermin D (GSDMD), as well as its impact on spheroid morphology in a three-dimensional (3D) cell culture model.
Materials and Methods: Spheroids were formed using 3D cell culture techniques and treated with increasing concentrations of doxorubicin (0.1–100 µM) for 24 and 48 hours. Spheroid number and diameter were analyzed using ImageJ v1.47. Caspase-1 and GSDMD protein levels were quantified by ELISA to assess the activation of pyroptotic pathways.
Results: Doxorubicin treatment led to a dose-dependent reduction in both spheroid number and size. At 100 µM, spheroid formation was completely inhibited and replaced by disorganized cell clusters. Caspase-1 and GSDMD protein levels increased significantly with higher doxorubicin concentrations, with peak expression observed at 25 µM; suggesting activation of inflammatory cell death pathways. No significant differences were found between 24- and 48-hour treatments.
Conclusion: Doxorubicin disrupts 3D spheroid structure and induces the expression of pyroptosis-related proteins in a concentration-dependent manner. These findings highlight its dual role in both impairing tumor architecture and activating inflammatory cell death mechanisms, providing insights into its therapeutic potential in solid tumors.
Keywords
Etik Beyan
Dear Editor,
In our study titled "Effect of doxorubicin on Caspase-1/GSDMD-mediated pyroptosis in MCF-7 breast cancer spheroids", we used a commercially obtained cell line, the name of the company from which the cell line was obtained and the registration number are provided in the ‘’Materials and Methods’’ section of the manuscript. Cells isolated directly from humans were not used; therefore, ethical committee approval is not required.
Kaynakça
- Ben-Dror J, Shalamov M, Sonnenblick A. The history of early breast cancer treatment. Genes (Basel) 2022;13(6):960.
- Xiong X, Zheng LW, Ding Y, Chen YF, Cai YW, Wang LP, et al. Breast cancer: pathogenesis and treatments. Signal Transduct Target Ther 2025;10(1):49.
- Hou X, Xu J, Wang Y, Zhao J, Guan Y, Yang X, et al. Triggering pyroptosis by doxorubicin-loaded multifunctional nanoparticles in combination with decitabine for breast cancer chemoimmunotherapy. ACS Appl Mater Interfaces 2024;16(43):58392-404.
- Wang Y, Gao W, Shi X, Ding J, Liu W, He H, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 2017;547(7661):99-103.
- Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, et al. Gasdermin E suppresses tumor growth by activating anti-tumor immunity. Nature 2020;579(7799):415-20.
- Fang Y, Tian S, Pan Y, Li W, Wang Q, Tang Y, et al. Pyroptosis: a new frontier in cancer. Biomed Pharmacother 2020;121:109595.
- Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J, et al. The role of pyroptosis in cancer: pro-cancer or pro-host? Cell Death Dis 2019;10(9):650.
- Yang F, Bettadapura SN, Smeltzer MS, Zhu H, Wang S. Pyroptosis and pyroptosis-inducing cancer drugs. Acta Pharmacol Sin 2022;43(10):2462-73.
Ayrıntılar
Birincil Dil
İngilizce
Konular
Kanser Hücre Biyolojisi , Histoloji ve Embriyoloji
Bölüm
Araştırma Makalesi
Yayımlanma Tarihi
8 Aralık 2025
Gönderilme Tarihi
26 Nisan 2025
Kabul Tarihi
19 Haziran 2025
Yayımlandığı Sayı
Yıl 2025 Cilt: 64 Sayı: 4