Sodium orthovanadate inhibits growth and triggers apoptosis of human anaplastic thyroid carcinoma cells in vitro and in�vivo

Abstract

Vanadium and its compounds exhibit concentration- and time-dependent anticancer effects on various types of tumor; however, the effects of sodium orthovanadate (SOV) on anaplastic thyroid carcinoma (ATC) have not yet been reported. In the present study, the anticancer effects of SOV on ATC were evaluated. In vitro experiments, including cell viability assays, plate colony formation assays, cell cycle analysis and apoptosis analysis were used to study the role of SOV in ATC. Using in vivo experiments, the effects of SOV on the growth and apoptosis of an ATC-xenograft tumor were studied by comparing the SOV-treatment with the control group. The results revealed that treatment of the human ATC cell line 8505C with SOV inhibited cell viability, induced G 2 /M phase cell cycle arrest, stimulated apoptosis and reduced mitochondrial membrane potential in a concentration-dependent manner. These findings were confirmed in vivo in a nude mouse ATC xenograft model. In conclusion, the present study demonstrated that SOV inhibited human ATC by regulating proliferation, cell cycle progression and apoptosis, thus suggesting that SOV may be considered a novel option for the treatment of ATC.

Molecular and Cellular Mechanisms of Cytotoxic Activity of Vanadium Compounds against Cancer Cells

“…Contrary to this study, other phenanthroline-based vanadium complex (73 and 74) caused a G0/G1 phase cell cycle arrest in the same type of cancer cell lines [82]. Additionally, G0/G1 phase cell cycle arrest, induced by organic vanadium complexes (75)(76)(77)(78), was shown in human neuroblastoma cells [83]. Cell cycle arrest in S phase has been determined in esophageal squamous carcinoma cell lines treated by sodium vanadate (61) [84].…”

“…Additionally, cell cycle disruption with simultaneous ROS generation was shown in lung carcinoma [47] and osteosarcoma cell lines [61]. [75]. Interestingly, the same vanadium salt (61) decreased the expression of cyclin D1 and increased the expression of p21 protein in papillary thyroid carcinoma-derived cells; however, the cell cycle profile was similar to the untreated cells [76].…”

“…Importantly, the results revealed that ROS-mediated degradation of cdc25C is responsible for vanadate-induced G 2 /M cell cycle arrest [74]. Furthermore, sodium orthovanadate (61) induced G 2 /M phase cell cycle arrest in a human thyroid carcinoma cell line [75]. Interestingly, the same vanadium salt (61) decreased the expression of cyclin D1 and increased the expression of p21 protein in papillary thyroid carcinoma-derived cells; however, the cell cycle profile was similar to the untreated cells [76].…”

“…Induction of apoptotic cell death by vanadium-based compounds is well established. Sodium orthovanadate (Na 3 VO 4 ) (61) induced apoptosis in the oral squamous cell carcinoma cell line [88] as well as in human anaplastic thyroid carcinoma cells [75]. Moreover, orthovanadate (61) induced typical features of apoptosis including DNA fragmentation, loss of mitochondrial membrane potential and activation of caspase-3 in thyroid cancer cells harboring RET/PTC1 (oncogenic chromosomal rearrangements) [76].…”

Vanadium in the environment as a risk factor causing negative modification of cell death (scientific review) UDC: 616-097

“…Между тем многие вопросы, касающиеся, возможно, новых механизмов запуска и изменения клеточной гибели ванадием, остаются дискуссионными. Ряд исследователей продемонстрировали апоптоз-индуцирующие свойства у ванадия и способность инициировать некроз [54,[58][59][60]. Однако другие ученые доказали способность ванадия ингибировать реализацию апоптоза [61].…”