Fucosterol exerts antiproliferative effects on human lung cancer cells by inducing apoptosis, cell cycle arrest and targeting of Raf/MEK/ERK signalling pathway

Mao, Zhangfan; Shen, Xiaoling; Dong, Ping; Liu, Gaoli; Pan, Shize; Sun, Xiangran; Hu, Haifeng; Li, Pan; Huang, Jie

doi:10.1016/j.phymed.2018.12.032

Cited by 45 publications

(26 citation statements)

References 21 publications

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“…Grb2, which regulates angiogenesis and cell movement, is highly overexpressed in tumors and may be useful as a target for anticancer agents. In the present study, we found Grb2 can be targeted by fucosterol, and activate the Raf / MEK / ERK pathway to achieve the purpose for treating NSCLC [43,[58][59][60].…”

Section: Discussionmentioning

confidence: 61%

“…Meanwhile, the PI3K-Akt signaling pathway participates in the regulation of cell cycle progression [40][41][42]. According to this map, we found the three signaling pathways can jointly activate the Raf / MEK / ERK signaling pathway which was reported playing an antiproliferation role in curing cancer [43]. More importantly, the downstream pathway-Raf / MEK / ERK signaling pathway mainly activated by GRB2 to regulate cell proliferation and migration.…”

Section: Analysis Of An Integrated Pathway Mapmentioning

confidence: 91%

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Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

Lin

et al. 2020

Preprint

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Background It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

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Section: Discussionmentioning

confidence: 61%

Section: Analysis Of An Integrated Pathway Mapmentioning

confidence: 91%

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

Lin

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Meanwhile, the PI3K-Akt signaling pathway participates in the regulation of cell cycle progression [40][41][42]. According to this map, we found the three signaling pathways can jointly activate the Raf / MEK / ERK signaling pathway which was reported playing an anti-proliferation role in curing cancer [43]. More importantly, the downstream pathway-Raf / MEK / ERK signaling pathway mainly activated by GRB2 to regulate cell proliferation and migration.…”

Section: Analysis Of An Integrated Pathway Mapmentioning

confidence: 91%

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

Lin

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

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“…In addition, fucosterol 23 (40 mg/kg b.w.) reduced Ki-67 expression, an indicator of cell proliferation, by 60%, and increased cleaved caspase-3 levels by more than 100%, which indicates that 23 acts in the tumor cells by simultaneously decreasing their proliferation and enhancing their apoptosis [148].…”

Section: Fucosterolmentioning

confidence: 96%

“…This phytosterol presents antitumor activity in vivo, with a dosage of 40 mg/kg (b.w. ), reducing about 75% of tumor weight and 50% of tumor volume after six weeks in lung cancer xenografted C57 BL/6 mice model [148]. In addition, fucosterol 23 (40 mg/kg b.w.)…”

Section: Fucosterolmentioning

confidence: 99%

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

et al. 2019

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Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.Studies focusing on the preparation of macroalgae extracts and their chemical characterization revealed a large range of seaweed compounds with very interesting biological activities including antitumor, anti-inflammatory, antimicrobial, antidiabetic, antivirus, antihypertensive, fat-lowering, and neuroprotective activities [12][13][14][15].The large volume of studies proving the seaweed compound activities in in vitro systems [16][17][18][19] hints the need for further advancements in the knowledge about macroalgae compound efficiency in living systems (in vivo) and their use in the development of pharmaceuticals. In vitro studies are very relevant and yield very important information, but they only represent the first step of a long process, and the results obtained rarely reveal anything about the effects of a compound in vivo, because the responses observed in vitro can be magnified, diminished, or totally different in a more complex and integrated system. In fact, in vivo studies and clinical trials are those which contribute most to truly understanding the real potential of compounds as future pharmaceuticals.In this regard, the present work intends to present insight into the results obtained in the last few years regarding secondary metabolites, such as phlorotannins, halogenated compounds, fucoxanthin, and fucosterol isolated from macroalgae, involved in in vivo studies and clinical trials, identifying the research opportunities and knowledge gaps, to valorize these compounds and their natural resources. The intention is not to present an exhaustive survey of all published works, but rather a selection of authors based on the following criteria: in-depth studies involving pure compounds most characteristic f...

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Fucosterol exerts antiproliferative effects on human lung cancer cells by inducing apoptosis, cell cycle arrest and targeting of Raf/MEK/ERK signalling pathway

Cited by 45 publications

References 21 publications

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

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