Abstract 184: Effects of the magnetic-organic compound Fe(salen) on anaplastic thyroid cancer cells
Authors: Tamura Shuzo , Oshima Takashi , Kamiya Mariko , Amano Shinya , Aoyama Toru , Nakayama Hirotaka , Suganuma Nobuyasu , Sato Tsutomu , Harada Hiroshi , Shiozawa Manabu , Yoshikawa Takaki , Miyagi Yohei , Rino Yasushi , Masuda Munetaka 
Published: July 2017

Introduction Although anaplastic thyroid cancer (ATC) is a rare disease, it is a cancer with one of the worst prognoses. Even in patients who receive multidisciplinary treatment, the 1-year survival rate is less than 30%. Because about 50% of patients with ATC die of airway obstruction, control of local progression is very important in the management of ATC. Novel treatments for ATC, especially those that can control local disease, are expected to emerge. Recently, several studies have reported that the magnetic organic compound μ-oxo N,N-bis(salicylidene)ethylenediamine iron (Fe(salen)) is effective against malignant melanoma and lingual cancer. Fe(Salen) itself is magnetic and might be effective as a local treatment by externally applying a magnetic field. Fe(salen) thus has the potential to become a novel treatment for ATCs. In this study, we evaluated uselessness of Fe(salen) as an anticancer drug for ATC.

Methods The in vivo anticancer effect of Fe(salen) against ATC cell lines (KTA1, KTA2, TTA2, TTA3, 8305c, 8505c) was evaluated by XTT assay. In addition, the effectiveness of combined therapy with paclitaxel, which is currently a standard chemotherapy for ATCs, was evaluated by the Chou and Talalay method. Colony formation assay was performed to evaluate differences in effects depending on the order of drug administration. In addition, to clarify the mechanism of Fe(salen) on cancer cells, changes in the cell cycle after Fe(salen) treatment were examined by flow cytometry.

Results Fe(salen) showed anticancer activity with an IC50 value of less than 100μM against KTA1, KTA2, TTA2, TTA3, 8305c, and 8505c cells. In particular, the IC50 values were less than 10 μM against TTA3 (8.82±4.58 μM) and 8305c (7.06±4.11 μM) cells. Combination therapy with paclitaxel had a synergistic effect, with a combination index of less than 1. No significant difference was detected in anticancer effect depending on the order of drug administration. G2/M cell cycle arrest was observed in 8305c cells on flow cytometry after Fe(salen) treatment.

Conclusion Our results showed that Fe(salen) has an anticancer effect on ATC cells and that Fe(salen) and paclitaxel have synergistic activity. We will evaluate the in vivo effectiveness of Fe(salen) treatment in an orthotopic mouse model, focusing on local control achieved by applying a magnetic field.

Citation Format: Shuzo Tamura, Takashi Oshima, Mariko Kamiya, Shinya Amano, Toru Aoyama, Hirotaka Nakayama, Nobuyasu Suganuma, Tsutomu Sato, Hiroshi Harada, Manabu Shiozawa, Takaki Yoshikawa, Yohei Miyagi, Yasushi Rino, Munetaka Masuda. Effects of the magnetic-organic compound Fe(salen) on anaplastic thyroid cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 184. doi:10.1158/1538-7445.AM2017-184