Euphorbia factor L1 reverses ABCB1‐mediated multidrug resistance involving interaction with ABCB1 independent of ABCB1 downregualtion

Zhang, Jian Ye; Mi, Yan Jun; Chen, Shu Peng; Wang, Fang; Liang, Yong; Zheng, Lichun; Shi, Cheng; Tao, Liyuan; Chen, Li Ming; Chen, Hubiao; Li, Fu

doi:10.1002/jcb.23021

Cited by 24 publications

(23 citation statements)

References 32 publications

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“…In several studies (Jiao et al, 2015; Zhang et al, 2013; Zhang et al, 2011) using human tumor MDR cells, compounds 1 and 3 , as well as analogues of 3 , have exhibited MDR reversal ability. Compounds 2 and 3 were suggested to act as modulators of P-gp, as both compounds could stimulate P-gp ATPase activity (Duan et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris

et al. 2018

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Analysis of the screening data compared with compound structures suggested that the substitutions at C-3, C-5, C-7, and C-15 are critical for cytotoxicity, as well as cell type-selectivity. Furthermore, results of cytotoxic mechanism analysis demonstrated for the first time that compounds 3 and 5 disrupted normal cell cycle progression, whereas compounds 2‒5 induced obvious actin filament aggregation, as well as partial interference of the microtubule network.

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Section: Resultsmentioning

confidence: 99%

Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris

et al. 2018

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“…Cancer chemotherapy offers effective treatment and developing novel anticancer drugs is a promising strategy to overcome cancer [ 28 , 29 ]. More and more evidence suggests that the success of anti-tumor chemotherapy depends on the discovery and development of novel drugs [ 23 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…As part of ongoing research, we have exhaustively investigated Caper Euphorbia Seed, examining the chemical isolation and structure identification of its components and their pharmacological aspects [ 20 , 21 , 22 , 23 ]. During these studies, lathyrol-3-phenylacetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed.…”

Section: Introductionmentioning

confidence: 99%

Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate

et al. 2017

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Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.

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“…It has been widely used for thousands of years for the treatment of warts and tumors [17], antibacterial activity [18], antiviral [19,20], anti-in ammation activity [21,22], anti-proliferative, antitumor-promoting and apoptosis inducing activities [23][24][25], and et al The main compounds of the ES include Lathyrane-type, diterpenoids, Ingenane-type, diterpenoids, Coumarins, etc. Many studies have been found that Euphorbia diterpenes can be regarded as effective lead compounds for the reversal of MDR [26][27][28]. It can be seen that ES have certain development value.…”

Section: Introductionmentioning

confidence: 99%

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

Song

Guo

Sun

et al. 2020

Preprint

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Background: Leukemia was listed by the World Health Organization as one of the five most intractable diseases in the world. The multi-drug resistance (MDR) of leukemia cells limits the efficacy of anti-tumor drugs and is the major reason for the chemotherapy failure and recurrence of leukemia chemotherapy. Some studies have shown that Euphorbiae semen (ES) possesses the characteristics of new therapeutic drugs for MDR. However, the molecular mechanisms and active compounds have not yet been fully clarified. Therefore, there is a need for explore its active compounds and demonstrate its mechanisms through network pharmacology and molecular docking technology.Method: First, the TCMSP database was searched and screened the active compounds of the ES, supplemented with compounds verified by literature, so as to further identify the core compounds in the active ingredient. Simultaneously, the TCMSP and Swiss database were searched to the targets of active compounds, and the targets of reverses leukemia multidrug resistance (RL-MDR) were screened in the relevant databases, such as GeneCards and DrugBank. Then, the targets of active compounds were intersected with RL-MDR targets to obtain potential targets of ES acting on MDR. The compound–target network was constructed by Cytoscape. The target protein–protein interaction network was built using STRING and Cytoscape database. Second, the R language and DAVID database were used to analyse Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment. Finally, molecular docking method was utilized to investigate the binding activity between the core targets and the active compounds of ES.Results: Compound–target network mainly contained 22 compounds and 81 corresponding targets. Finally, seven components in ES were selected and 10 core targets were identified; Key targets contained JUN, CASP3, MAOA, AR, PPARG, DRD2, ADRA2A, CHRM2, PTGS2 and MAPK14. GO enrichment analysis indicated the main biological functions of potential genes of ES in the treatment of MDR. KEGG pathway enrichment analysis showed the main pathways, mainly including apoptosis, pathways in cancer, p53 signaling pathway, VEGF signaling pathway, TNF signaling pathway and PI3K–Akt signaling pathway. Finally, we chose the top 10 common targets for molecular docking with the 7 active compounds of ES. The results of molecular docking indicated that the compounds of ES, which had good affinity with targets. Conclusion: The molecular mechanism of ES in the treatment of MDR showed the synergistic reaction of multi-compound, multi-target, and multi-pathway of traditional Chinese medicine, which provided ideas for further clinical research.

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Euphorbia factor L1 reverses ABCB1‐mediated multidrug resistance involving interaction with ABCB1 independent of ABCB1 downregualtion

Cited by 24 publications

References 32 publications

Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris

Mechanism of action of cytotoxic compounds from the seeds of Euphorbia lathyris

Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate

Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

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