Antroquinonol from Antrodia Camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1- and AKT-NF-κB-dependent MMP-9 and epithelial-mesenchymal transition expressions

Lee, Wai-Theng; Lee, Tzong‐Huei; Cheng, Chia‐Hsiung; Chen, Ku‐Chung; Chen, Yen-Chou; Lin, Chun-Yu

doi:10.1016/j.fct.2015.01.012

Cited by 57 publications

(51 citation statements)

References 38 publications

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“…Reportedly, MEK/ERK and PI3K/AKT extensively regulate important transcriptional and post-transcriptional events and function as an important EMT modulator [16,17]. Results from the MEK/ERK and PI3K/AKT kinase inhibitors showed the GSK1120212, BEZ235, and MK2206 individually prohibited the increase of Twist, N-cadherin, MMP9, and α-SMA, while the DMSO control cannot, suggesting MEK/ERK and PI3K/AKT pathway was involved in CCL19-induced EMT.…”

Section: Discussionmentioning

confidence: 91%

CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

Xu³

et al. 2015

Tumor Biol.

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As reported, the CC chemokine receptor 7 (CCR7) trigger a series of signaling cascades in the epithelial-mesenchymal transition (EMT) of some malignancies. Meanwhile, Twist promotes EMT in pancreatic ductal adenocarcinoma (PDAC) progression. Here, effects of Twist on CCR7-induced EMT in the PDAC were investigated in detail. The immunohistochemistry was used to detect the expression of Twist, and then, in vitro assays were applied. The expression rate of Twist was 72.0 % in PDAC samples and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When PDAC cell line PANC1 was subjected to CCL19 stimulation, the expression of p-ERK, p-AKT, Twist, N-cadherin, MMP9, and α-smooth muscle actin (α-SMA) was induced, while the GSK1120212, BEZ235, and MK2206 prohibited the increase of Twist and EMT biomarkers. For another thing, the si-Twist treatment attenuated CCL19-stimulated EMT occurrence, migration, and invasion phenotypes of PANC1 cells. In conclusion, CCR7 pathway up-regulates Twist expression via ERK and PI3K/AKT signaling to manage the EMT of PDAC. Our work allows for clinical gene or protein-targeted regimen of PDAC patients in the near future.

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Section: Discussionmentioning

confidence: 91%

CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

Xu³

et al. 2015

Tumor Biol.

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“…Besides, both p-Akt and p-Erk were found to be overexpressed in ZR-75-1 as well as BT-474 cells after fulvestrant treatment but notably decreased from these levels when combined with trastuzumab, implying that the combination of trastuzumab and fulvestrant significantly prevented fulvestrant from increasing the levels of these proteins in HR+/HER2+ breast cancer. Since the activation of PI3K/Akt/mTOR and MAPK/Erk signaling pathways correlates with worse clinical outcomes in breast cancer[47,48], our results suggest that HR+/HER2+ breast cancer patients receiving co-targeted therapies including trastuzumab and fulvestrant in combination could probably have a better prognosis than those receiving fulvestrant alone.…”

Section: Discussionmentioning

confidence: 99%

An Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin) and Fulvestrant (Falsodex), as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts

Chen

Weng

et al. 2017

PLoS ONE

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PurposeTo investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue.MethodsCells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied. The distribution and abundance of the proteins p-Akt and p-Erk expressed in these cells in response to single agents or combinatorial treatment were also investigated. In addition, the effects of trastuzumab and fulvestrant, either as single agents or in combination on tumor growth as well as on expression of the protein p-MED1 expressed in in vivo mouse xenograft models was also examined.ResultsCell proliferation was increasingly inhibited by trastuzumab or fulvestrant or both, with a CI<1 and DRI>1 in both human cell lines. The rate of apoptosis increased only in the BT-474 cell line and not in the ZR-75-1 cell line upon treatment with fulvestrant and not trastuzumab as a single agent (P<0.05). Interestingly, fulvestrant, in combination with trastuzumab, did not significantly alter the rate of apoptosis (in comparison with fulvestrant alone), in the BT-474 cell line (P>0.05). Cell accumulation in the G1 phase of cell cycle was investigated in all treatment groups (P<0.05), and the combination of trastuzumab and fulvestrant reversed the effects of fulvestrant alone on p-Akt and p-Erk protein expression levels. Using ZR-75-1 or BT-474 to generate in vivo tumor xenografts in BALB/c athymic mouse models, we showed that a combination of both drugs resulted in a stronger inhibition of tumor growth (P<0.05) and a greater decrease in the levels of activated MED1 (p-MED1) expressed in tumor issues compared with the use of either drug as a single agent.ConclusionsWe demonstrate that the administration of trastuzumab and fulvestrant in combination results in positive synergistic effects on both, ZR-75-1 and BT-474 cell lines. This combinatorial approach is likely to reduce physiological side effects of both drugs, thus providing a theoretical basis for the use of such combination treatment in order to resolve HR+/HER2+ triple positive breast cancer that has previously been shown to be resistant to endocrine treatment alone.

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“…It was chemically characterised as a unique, unstable quinonol nucleus with a sesquiterpene side chain. Studies on the biological activity of antroquinonol suggest that it possesses potent and selective anticancer effect between cancer cells and normal cells (Ho et al, 2014;Lee et al, 2015;Yang et al, 2013). Most of the previous studies related to antroquinonol mainly only focused on its biological and pharmacological activities and there are very few investigations on the regulatory mechanism of its biosynthesis pathway.…”

Section: Introductionmentioning

confidence: 99%

A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata

Zhang

et al. 2016

Journal of Functional Foods

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Antroquinonol from Antrodia Camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1- and AKT-NF-κB-dependent MMP-9 and epithelial-mesenchymal transition expressions

Cited by 57 publications

References 38 publications

CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

An Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin) and Fulvestrant (Falsodex), as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts

A mechanistic study on the biosynthetic regulation of bioactive metabolite Antroquinonol from edible and medicinal mushroom Antrodia camphorata

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