Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

Acute Onset Methimazole-Induced Arthralgia and Skin Rash / 대한갑상선학회지

Methimazole, a type of thionamide, is used to treat hyperthyroidism. Several adverse effects of thionamides have been reported. The representative minor adverse effects are arthralgia, skin rash, and gastric intolerance. Methimazole is reported to induce 1-6% of arthralgia cases. These patients begin to suffer from arthralgia from 1 month to 2 years after methimazole treatment. Here, we present a patient with acute onset methimazole-induced arthralgia and skin rash. At 2 days after starting methimazole treatment, a 57-year-old female developed arthralgia and a skin rash on her right leg, which subsequently spread to her left leg and right arm, and she stopped taking the medication. The patient was admitted to the rheumatology department of Ulsan University Hospital, where laboratory tests and a skin biopsy were performed to ascertain whether she had a rheumatic disorder. The skin biopsy revealed nonspecific inflammation. At 2 days after stopping methimazole treatment, the arthralgia and skin rashes had improved and methimazole treatment was recommenced. However, the same symptoms developed within 1 day. Therefore, methimazole treatment was again stopped and the symptoms disappeared.