Molecular targets of β-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review.

β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of β-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of β-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. β-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, β-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies have shown that β-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, β-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied and identified.

Zhai B ，Zhang N ，Han X ，Li Q ，Zhang M ，Chen X ，Li G ，Zhang R ，Chen P ，Wang W ，Li C ，Xiang Y ，Liu S ，Duan T ，Lou J ，Xie T ，Sui X ... -  《-》

β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis.

Liu J ，Zhang Y ，Qu J ，Xu L ，Hou K ，Zhang J ，Qu X ，Liu Y ... -  《BMC CANCER》

β-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells.

β-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of β-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated. Cell viability and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by Western blotting. Autophagy was evaluated under fluorescence microscopy and transmission electron microscopy. β-Elemene inhibited the viability of A549 cells in a dose-dependent manner. This suppression of cell viability was due to the induction of apoptosis. Further study showed that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a robust autophagy. The autophagy was characterized by the accumulation of punctate LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3-II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with chlorochine significantly enhanced the antitumour effect of β-elemene. Our data indicated that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which resulted in apoptosis as well as protective autophagy. A combination of β-elemene with autophagy inhibitor might be an effective therapeutic option for advanced NSCLC.

Liu J ，Hu XJ ，Jin B ，Qu XJ ，Hou KZ ，Liu YP ... -  《-》

B-cell lymphoma-2 over-expression protects δ-elemene-induced apoptosis in human lung carcinoma mucoepidermoid cells via a nuclear factor kappa B-related pathway.

Xie CY ，Yang W ，Ying J ，Ni QC ，Pan XD ，Dong JH ，Li K ，Wang XS ... -  《-》

β-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway.

β-Elemene is a natural agent extracted from the traditional Chinese herbal medicine Curcuma wenyujin that is a promising novel plant-derived drug with broad-spectrum anticancer activity. Our previous study identified an enhanced capacity for metastasis in multidrug resistant (MDR) gastric cancer and breast cancer cells. However, the anti-metastatic effects of β-Elemene on MDR cancer cells remain unknown. In this study, we posit the hypothesis that β-elemene possesses antimetastatic effects on MDR cancer cells. Cell viability assay was used to assess the resistance of SGC7901/ADR cells and the cytotoxic effects of β-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of β-Elemene. MicroRNA microarray analysis was used to explore potential regulated miRNAs. Luciferase reporter assay was used to identify the direct target. Human MMP antibody array, western blot, immunoprecipitation, qRT-PCR analyses and immunohistochemistry were conducted to investigate the underlying anti-metastasis mechanism of β-Elemene. In this study, we found that β-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that β-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that β-Elemene upregulated Cbl-b expression, resulting in inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that β-Elemene upregulated Cbl-b by inhibiting miR-1323 expression. Finally, we found that numbers of metastatic tumor nodules were significantly decreased in the lungs of nude mice after β-Elemene treatment. Our results suggested that β-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.

Deng M ，Liu B ，Song H ，Yu R ，Zou D ，Chen Y ，Ma Y ，Lv F ，Xu L ，Zhang Z ，Lv Q ，Yang X ，Che X ，Qu X ，Liu Y ，Zhang Y ，Hu X ... -  《-》