Dihydrotanshinone exerts antitumor effects and improves the effects of cisplatin in anaplastic thyroid cancer cells

Abstract

Anaplastic thyroid cancer (ATC) is the most aggres- sive type of thyroid cancer and is responsible for 20-50% of thyroid cancer-associated deaths. The absence of response to conventional treatments makes the search for novel therapeu- tics a clinical challenge. In the present study, the effects of 15,16-dihydrotanshinone I (DHT), a tanshinone extracted from Salvia miltiorrhiza Bunge (Danshen), which has previously been shown to possess anticancer activity, were examined in two human ATC cell lines. DHT significantly reduced cell viability, which was coupled with an increase in apoptosis. DHT administration also reduced the colony-forming ability and proliferation of these cells in soft agar and downregulated the expression of epithelial-to-mesenchymal transition-related genes. In addition, DHT significantly reduced MAD2 expres- sion, a target of HuR with a relevant role in ATC. Finally, cotreatment with cisplatin and DHT has a greater effect on cell viability than each compound alone. In conclusion, to the best of our knowledge, the present study is the first to demonstrate that DHT exerts antitumor effects on ATC cells by reducing MAD2 expression levels. Moreover, a synergistic effect of DHT with cisplatin was shown. Further in vivo studies are required to assess this phytochemical compound as a potential adjuvant for the treatment of ATC.