Doxorubicin Induces Fas-Mediated Apoptosis in Human Thyroid Carcinoma Cells

Abstract

Doxorubicin remains the most extensively used drug in the chemotherapy of thyroid cancer. However, drug resistance often limits the efficacy of chemotherapy in clinical practice. Several anticancer drugs exert their cytotoxic effect by triggering Fas-mediated apoptosis in some cell types. However, no investigations have been conducted to determine whether doxorubicin causes apoptosis in thyroid carcinomas. In the present study, we assessed the cytotoxic and apoptotic effects of doxorubicin on two thyroid cancer cell lines (FTC 238 and FTC 133). Cytotoxic effects of doxorubicin were evaluated by a 3-(4,5 dimethylthiazol-2yl) 2-5 diphenyltetrazolium bromide (MTT) assay. Apoptosis was quantified by fluorescein isothiocyanate-conjugated annexin V/flow cytometric analysis and by DNA fragmentation. Fas expression was measured by flow cytometric analysis. After a 24-hour incubation, doxorubicin induces a dose-dependent cytotoxicity in the two cell lines. Treatment with doxorubicin (0.5 and 1 microM) for 24 hours induced cell apoptosis and upregulated Fas expression. A significant correlation was found between the fluorescence intensity values obtained with annexin V staining and those observed for Fas expression (r = 0.996; p < 0.001 or r = 0.957; 0.02 < p < 0.05 for FTC 238 or FTC 133 cells, respectively). In conclusion, doxorubicin exerts its cytotoxic effects, at least partly, through Fas-mediated apoptosis in thyroid cancer cells. These results may have clinical implications for thyroid cancer therapy.

Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin

“…Doxorubicin is the most effective single agent against ATC. Although doxorubicin causes cell death, at least in part, by inducing apoptosis in ATC cells (23), the mechanism underlying its pharmacological efficacy is not been fully understood. HDACI sensitizes ATC cells to doxorubicin, which induces apoptosis by reducing histone deacetylase activity and inducing hyperacetylation of histone (24).…”

Intracellular delivery of doxorubicin encapsulated in novel pH-responsive chitosan/heparin nanocapsules

“…Doxorubicin forms complexes with DNA by intercalation between base pairs, and inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II activity. 23 After 5 hours of incubation, the cells lines show blebs which are indicative of apoptosis suggesting the cytotoxic activity of doxorubicin 24 ( Figure 5 [3C]). For the purpose of comparison with doxorubicin-loaded nanocapsules, confocal images of free doxorubicin loaded into the cells are also provided ( Figure 6).…”

In-vitro Application of Doxorubicin Loaded Magnetoplasmonic Thermosensitive Liposomes for Laser Hyperthermia and Chemotherapy of Breast Cancer

“…In Figure 12, membrane blebbing can be identified which is characteristic of apoptotic cells [41]. Redistribution of phosphatidylserine from the inner to the outer plasma membrane leaflet has become one of the most widely used markers for apoptotic cells in mammals.…”