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

Abstract

Anaplastic thyroid cancer (ATC) is the most aggressive 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 therapeutics 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 expression, 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.

Effects of Dihydrotanshinone I on Proliferation and Invasiveness of Paclitaxel-Resistant Anaplastic Thyroid Cancer Cells

“…Lee et al demonstrated that DHT treatment induces a decrease in cell population in the Gl phase, an increase in the S phase cells and apoptosis in erythroleukemia cells resistant to Adriamycin [ 44 ]. These results are consistent with those we observed in ATC cells treated with DHT [ 27 ], suggesting a similar mechanism underlying the effects observed in ATC-PTX cells.…”

“…In particular, we demonstrated that DHT, a lipophilic abietane diterpene compound extracted from the dried root of Salvia miltiorrhiza , has an antitumor action in ATC cell lines, and this action is in part mediated by the regulation of the HuR-MAD2 axis known to be involved in the proliferation, survival and aggressiveness of this tumor [ 42 , 43 ]. In this study, we evaluated the effects of DHT on ATC cell lines resistant to Paclitaxel and found that DHT was effective in reducing cell viability in SW1736-PTX and 8505C-PTX cells with an EC50 absolutely comparable with that observed in non-resistant ATC cells in our previous work [ 27 ]. Lee et al demonstrated that DHT treatment induces a decrease in cell population in the Gl phase, an increase in the S phase cells and apoptosis in erythroleukemia cells resistant to Adriamycin [ 44 ].…”

“…Among the phytochemicals tested against ATC cancer cells [ 21 , 22 , 23 ], particular attention has been focused on 15,16-dihydrotanshinone I (DHT), a tanshinone extracted from Salvia miltiorrhiza Bunge (Danshen), one of the most frequently prescribed herbs in traditional Chinese medicine [ 24 ]. DHT has not only shown promising anticancer effects in numerous in vitro models of many types of cancer, including ATC [ 25 , 26 , 27 ], but has also been tested in animal models, confirming its ability to inhibit tumor growth with no adverse effects on healthy tissues [ 28 , 29 ]. Moreover, Hu et al demonstrated that DHT plays an important role in circumventing colon cancer cell resistance by down-regulating ABCB1 expression and inhibiting its ATPase activity, thereby increasing intracellular accumulation of the transporter substrate anticancer drugs [ 30 ].…”

Role of m6A RNA Methylation in Thyroid Cancer Cell Lines

“…Because of its dismal prognosis, it is responsible for 40–50% of total thyroid cancer-related deaths [ 30 ]. In recent years, research has produced great efforts in an attempt to find an effective treatment against ATC, such as the use of taxane, dabrafenib, or trametinib (in patients harboring the BRAF p.V600E mutation) [ 31 ]; natural compounds such as DHT [ 32 ]; or molecules that can alter epigenetic pathways [ 33 ]. However, there is still no standardized and effective treatment for this type of malignancy, partly because ATC cells are able to evade most therapeutic strategies by developing chemoresistance [ 32 ].…”

Dihydrotanshinone I Specifically Inhibits NLRP3 Inflammasome Activation and Protects Against Septic Shock In Vivo

“…Dihydrotanshinone I (DHT) is a natural compound extracted from Danshen. According to the reports, DHT has antitumor ( Allegri et al, 2021 ), anti-inflammatory ( Wang et al, 2020 ), and immunomodulatory effects ( Wang et al, 2020 ). Evidence has emerged that DHT attenuates crystalline silica–induced lung inflammation by regulating the immune response and inhibiting STAT1/STAT3 ( Wang et al, 2020 ).…”