Antineoplastic effect of doxorubizen in vitro in continuous and primary human anaplastic thyroid cancer cells
Giusy Elia1, Silvia Martina Ferrari2, Iryna Tkachenko3
1Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
Purpose:
New drugs are needed for the therapy of anaplastic thyroid cancer (ATC). This study aims to investigate doxorubizen (a dual-action structural hybrid (chimera) of doxorubicin (Dox) and DNA methylating drug temozolomide), in comparison with Dox, and alone or in combination with lenvatinib in ATC 8305C cells, and in primary human ATC cell cultures (pATC).
Methods:
We have investigated doxorubizen, Dox, and lenvatinib on 5 different pATC and in continuous 8305C cell line in vitro, evaluating their effect on cells proliferation by WST-1, apoptosis (Hoechst ad Annexin V assays) and migration (Chemicon QCM™ 96-well Migration Assay).
Results:
The results have demonstrated: (1) a significant antiproliferative and proapoptotic effect of doxorubizen in 8305C and in pATC; (2) a significant antiproliferative and proapoptotic effect of Dox in pATC, and in 8305C; (3) the antineoplastic effect of lenvatinib in 8305C and in pATC; (4) a stronger antiproliferative and proapoptotic effect of doxorubizen than that of Dox, or lenvatinib; (5) that doxorubizen induced an inhibition of migration in pATC stronger than that of Dox, or lenvatinib; (6) that doxorubizen is able to synergize in vitro with lenvatinib increasing the antiproliferative effect, while doxorubizen alone is the primary factor that promotes the proapoptotic impact.
Conclusion:
We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.
Insights
Doxorubizen, a novel drug combining doxorubicin and temozolomide, shows potent anti-cancer effects against anaplastic thyroid cancer cells. It effectively reduces proliferation, induces apoptosis, and inhibits migration, outperforming doxorubicin and lenvatinib alone and synergizing with lenvatinib.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited therapeutic options.
- Novel therapeutic strategies are urgently needed to improve patient outcomes.
Purpose of the Study:
- To investigate the efficacy of doxorubizen, a novel hybrid drug, against ATC.
- To compare doxorubizen with doxorubicin (Dox) and lenvatinib in ATC cell lines and primary cultures.
- To evaluate the synergistic potential of doxorubizen and lenvatinib.
Main Methods:
- In vitro assessment of doxorubizen, Dox, and lenvatinib in ATC 8305C cells and primary human ATC cultures.
- Evaluation of cell proliferation (WST-1 assay), apoptosis (Hoechst and Annexin V assays), and migration (Chemicon assay).
Main Results:
- Doxorubizen demonstrated significant antiproliferative and proapoptotic effects in both cell lines and primary cultures.
- Doxorubizen exhibited superior efficacy compared to Dox or lenvatinib in reducing proliferation and inducing apoptosis.
- Doxorubizen significantly inhibited cell migration and showed synergistic effects with lenvatinib in enhancing antiproliferative activity.
Conclusions:
- Doxorubizen exhibits potent in vitro antineoplastic activity against ATC.
- Doxorubizen demonstrates synergistic potential with lenvatinib, suggesting a promising therapeutic combination.
- These findings support further clinical investigation of doxorubizen for ATC treatment.
