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Published on: August 23, 2019
Beta-elemene inhibits differentiated thyroid carcinoma metastasis by reducing cellular proliferation, metabolism and
Lei Zhao1, Jian Wei1, Shiqi Wang1
1Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China.
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.
Insights
Beta (β)-elemene, a natural compound, effectively inhibits thyroid carcinoma growth by reducing cell proliferation, invasion, and angiogenesis. This study reveals its potential as a novel therapeutic agent for thyroid cancer.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Accelerated glycolysis is a hallmark of carcinoma, yet the anticancer mechanisms of beta (β)-elemene, which inhibits aerobic glycolysis, remain unclear for thyroid carcinoma.
- Investigating the efficacy and underlying mechanisms of β-elemene against differentiated thyroid carcinoma (DTC) is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To evaluate the antitumor effects of β-elemene on differentiated thyroid carcinoma (DTC) cell lines.
- To elucidate the mechanisms by which β-elemene exerts its anticancer effects, including its impact on cell proliferation, apoptosis, invasion, angiogenesis, and energy metabolism.
Main Methods:
- Differentiated thyroid carcinoma (DTC) cell lines were treated with varying concentrations of β-elemene.
- Cell viability, cell cycle, apoptosis, and invasion were assessed using CCK8 assays, flow cytometry, western blotting, and Transwell assays, respectively.
- Energy metabolism was measured using a Seahorse XF analyzer, and in vivo antitumor effects were evaluated in a nude mouse xenograft model.
Main Results:
- β-elemene significantly inhibited DTC cell proliferation and invasion in a dose- and time-dependent manner.
- The compound promoted apoptosis by increasing cleaved caspase-9 and decreasing BCL-2 expression, while also reducing angiogenesis via decreased VEGF expression.
- β-elemene markedly reduced oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic and respiratory capacities, indicating impaired cellular energy metabolism.
Conclusions:
- β-elemene demonstrates significant antitumor activity against thyroid carcinoma by inhibiting proliferation, invasion, and angiogenesis, and promoting apoptosis.
- The compound effectively suppresses both respiratory and glycolytic metabolism in human DTC cells.
- These findings highlight β-elemene as a promising novel therapeutic candidate for differentiated thyroid carcinoma.
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