Abstract
BACKGROUND: Accelerated glycolysis is a characteristic of carcinoma. The herb-derived compound, beta (β)-elemene, has shown promising anticancer effects against various tumors by inhibiting aerobic glycolysis. However, its activity against thyroid carcinoma and the mechanism is still unknown. METHODS: Differentiated thyroid carcinoma (DTC) cell lines, including papillary thyroid carcinoma (PTC) cell lines (IHH-4, TPC-1, K1), and follicular thyroid carcinoma (FTC) cell line (FTC133) were treated with different concentration of β-elemene. The viability of DTC cells was analyzed using the CCK8 method. Cell cycle and apoptosis analysis were performed by flow cytometry and western blotting. The cell invasion ability was evaluated in Transwell assays. Energy metabolism in living cells was measured using a Seahorse XF analyzer. The antitumor effects of β-elemene were analyzed in vivo in a nude mouse xenograft tumors model. RESULTS: CCK8 assays showed β-elemene significantly inhibited DTC cell proliferation in a dose- and time-dependent manner. β-elemene promoted cell apoptosis, with increased expression of cleaved caspase-9 and decreased BCL-2 expression. Transwell assays showed that β-elemene significantly inhibited the invasion ability of DTC cells. β-elemene also reduced angiogenesis by decreasing VEGF expression in DTC cells. β-elemene reduces the basal oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic capacity as well as maximal respiration and ATP production. Moreover, β-elemene inhibited tumor growth in a mouse xenograft model in vivo. CONCLUSIONS: In this study, we have provided the first evidence of the antitumor effects of β-elemene, which was shown to inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, inhibit cell invasion ability and reduce angiogenesis. Furthermore, we showed that β-elemene significantly inhibits the respiratory and glycolytic ability of human DTC cells. Thus, our findings show the potential of β-elemene as a novel treatment for DTC.