Yuanhuatine from Daphne genkwa selectively induces mitochondrial apoptosis in estrogen receptor α-positive breast cancer cells in vitro

Zhang, Yingying; Shang, Xiuli; Hou, Xuewen; Li, Lingzhi; Wang, Wei; Hayashi, Toshihiko; Zhang, Yan; Yao, Guo-Dong; Song, Shao‐Jiang

doi:10.1055/a-1013-1439

Cited by 14 publications

(7 citation statements)

References 27 publications

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“…2i-l). Our work showed that the IC50 of tamoxifen on MCF-7 cells (close to 15 µM) is close to that observed by Zhang et al [23]. Similarly, in agreement with our results, they observed that the MDA-MB-231 cells are resistant to tamoxifen.…”

Section: Eo771 Cells Are Sensitive To Anti-estrogen Treatmentssupporting

confidence: 93%

EO771, the first luminal B mammary cancer cell line from C57BL/6 mice

Naour

Diab

et al. 2020

Cancer Cell Int

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Background: Despite decades of therapeutic trials, effective diagnosis, many drugs available and numerous studies on breast cancer, it remains the deadliest cancer in women. In order to choose the most appropriate treatment and to understand the prognosis of the patients, breast cancer is divided into different subtypes using a molecular classification. Just as there remains a need to discover new effective therapies, models to test them are also required. Methods: The EO771 (also named E0771 or EO 771) murine mammary cancer cell line was originally isolated from a spontaneous tumour in C57BL/6 mouse. Although frequently used, this cell line remains poorly characterized. Therefore, the EO771 phenotype was investigated. The phenotype was compared to that of MCF-7 cells, known to be of luminal A subtype and to express estrogen receptors, as well as MDA-MB-231 cells, which are triple negative. Their sensitivity to hormonal treatment was evaluated by viability tests. Results: The EO771 were estrogen receptor α negative, estrogen receptor β positive, progesterone receptor positive and ErbB2 positive. This phenotype was associated with a sensitivity to anti-estrogen treatments such as tamoxifen, 4-hydroxy-tamoxifen, endoxifen and fulvestrant. Conclusions: On account of the numerous results published with the EO771 cell line, it is important to know its classification, to facilitate comparisons with corresponding types of tumours in patients. Transcriptomic and protein analysis of the EO771 cell line classified it within the luminal B subtype. Luminal B cancers correspond to one of the subtypes most frequently encountered in patients and associated with a poor prognosis.

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Section: Eo771 Cells Are Sensitive To Anti-estrogen Treatmentssupporting

confidence: 93%

EO771, the first luminal B mammary cancer cell line from C57BL/6 mice

Naour

Diab

et al. 2020

Cancer Cell Int

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“…A study performed by Siewiński et al indicated that positive expression of high molecular weight cysteine proteinase inhibitor was observed on the tumor cell surface in serous and endometrioid metastatic ovarian cancer [31]. A plenty of investigations also suggested that apoptotic process correlated with BC [32][33][34], which further supported our current predicted findings.…”

Section: Discussionsupporting

confidence: 89%

FKBP-related ncRNA-mRNA axis in breast cancer

Xiong

Chen²,

Zheng

et al. 2020

Preprint

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KEYWORDSbreast cancer; microRNA; long noncoding RNA; FK506-binding protein; bioinformatic analysis.3 Abstract Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely.FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings. Background Breast cancer (BC) is the most widespread and deadly non-cutaneous tumor in worldwide women[1]. 4 Early detection and comprehensive treatments, which consist of surgery, radiation, chemotherapy, endocrine therapy and targeted therapy, have significantly improved the prognosis in BC patients. However, BC is a heterogeneous disease of various different genetical, pathological, and clinical subtypes[2]. Even though intensive efforts have been made in both basic researches and clinical studies, it's still necessary to find more reliable markers to further improve therapeutics for BC patients.FK506-binding protein (FKBP) family in Homo...

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“…Traditional Chinese medicinal herbs and their active constituents have long been evaluated for the treatment of carcinomas, including TNBCs, due to their ability to target multiple oncogenic signaling pathways [ 34 ]. Yuanhuacine ( 1 ), one of the constituents of the medicinal plant Daphne genkwa , has been previously reported to have in vitro cytotoxic activity against over a dozen diverse human cancer cell lines at concentrations ranging from 1–27 µM [ 21 , 35 , 36 , 37 ]. This is in striking contrast to the single digit nanomolar potency we observed for this compound in cell lines that represent the BL2 subtype of TNBC; HCC1806 (IC 50 : 1.6 nM) and HCC70 (IC 50 : 9.4 nM).…”

Section: Discussionmentioning

confidence: 99%

Yuanhuacine Is a Potent and Selective Inhibitor of the Basal-Like 2 Subtype of Triple Negative Breast Cancer with Immunogenic Potential

Fermaintt

Peramuna

Cai

et al. 2021

Cancers

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The heterogeneity of triple negative breast cancer (TNBC) has led to efforts to further subtype this disease with the hope of identifying new molecular liabilities and drug targets. Furthermore, the finding that TNBC is the most inherently immunogenic type of breast cancer provides the potential for effective treatment with immune checkpoint inhibitors and immune adjuvants. Thus, we devised a dual screen to identify compounds from natural product extracts with TNBC subtype selectivity that also promote the expression of cytokines associated with antitumor immunity. These efforts led to the identification of yuanhuacine (1) as a potent and highly selective inhibitor of the basal-like 2 (BL2) subtype of TNBC that also promoted an antitumor associated cytokine signature in immune cells. The mechanism of action of yuanhuacine for both phenotypes depends on activation of protein kinase C (PKC), defining a novel target for the treatment of this clinical TNBC subtype. Yuanhuacine showed potent antitumor efficacy in animals bearing BL2 tumors further demonstrating that PKC could function as a potential pharmacological target for the treatment of the BL2 subtype of TNBC.

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Yuanhuatine from Daphne genkwa selectively induces mitochondrial apoptosis in estrogen receptor α-positive breast cancer cells in vitro

Cited by 14 publications

References 27 publications

EO771, the first luminal B mammary cancer cell line from C57BL/6 mice

EO771, the first luminal B mammary cancer cell line from C57BL/6 mice

FKBP-related ncRNA-mRNA axis in breast cancer

Yuanhuacine Is a Potent and Selective Inhibitor of the Basal-Like 2 Subtype of Triple Negative Breast Cancer with Immunogenic Potential

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