Preclinical Evidence that Arctigenin Effectively and Selectively Targets Clear Cell Renal Cell Carcinoma Via Suppressing EGFR and RhoA.

Clear cell renal cell carcinoma (ccRCC) has poor clinical outcomes and necessitates new treatment options. Epidermal growth factor receptor (EGFR) is a potential therapeutic target, due to the associations with various carcinomas' progression. Arctigenin, a natural compound of Arctium lappa, has bee...

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Publicado en:Nutrition & Cancer Vol. 75; no. 5; pp. 1373 - 1382
Autores principales: Dongcao Liu, Guang Zhou, Mingwei Xu
Formato: pictorial research tables/charts Journal Article
Publicado: Taylor & Francis Ltd 2023
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2023
      vid: 75
      iid: 5
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      pub: Taylor & Francis Ltd
      place: Philadelphia, Pennsylvania
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        10.1080/01635581.2023.2178920
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        atl: Preclinical Evidence that Arctigenin Effectively and Selectively Targets Clear Cell Renal Cell Carcinoma Via Suppressing EGFR and RhoA.
      aug:
        au:
          Dongcao Liu
          Guang Zhou
          Mingwei Xu
        affil: Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China
      sug:
        subj:
          Carcinoma, Renal Cell Drug Therapy
          Lignans Pharmacodynamics
          Antineoplastic Agents Pharmacodynamics
          Epidermal Growth Factor Receptors Drug Effects
          Carrier Proteins Drug Effects
          Plants, Medicinal
          Plant Extracts Pharmacodynamics
          Animal Studies
          Mice
          In Vivo Studies
          Immunoblotting
          Biochemistry
          Signal Transduction
          Cell Line, Tumor Drug Effects
          Cell Movement
          Cell Viability
          Sorafenib
          Drug Synergism
          Xenografts
          Antineoplastic Agents, Combined Therapeutic Use
          Drug Therapy, Combination
          Carcinoma, Renal Cell Physiopathology
          Disease Progression Prevention and Control
          Neoplastic Processes Prevention and Control
          Funding Source
      ab: Clear cell renal cell carcinoma (ccRCC) has poor clinical outcomes and necessitates new treatment options. Epidermal growth factor receptor (EGFR) is a potential therapeutic target, due to the associations with various carcinomas' progression. Arctigenin, a natural compound of Arctium lappa, has been shown to display anticancer abilities in various carcinomas. Cellular assays and combination studies were conducted using arctigenin and anti-ccRCC drugs. In vivo efficacy of arctigenin was determined using ccRCC xenograft mouse model. Immunoblotting and biochemistry analysis were applied to investigate the signaling affected by arctigenin. Arctigenin inhibits growth, migration, and survival of ccRCC cells while sparing normal kidney cells. Arctigenin acts synergistically with 5-FU and sorafenib but not temsirolimus in inhibiting ccRCC cells. Synergism of arctigenin with 5-FU and sorafenib was further shown in ccRCC xenograft mouse model. The combination of arctigenin with clinical anti-RCC drugs completely inhibits tumor growth without tumor progression even for an extended time period. Mechanistically, arctigenin inhibits migration in a RhoA-dependent manner while inhibits growth via suppressing EGFR-mediated signaling pathways. Our findings suggest that arctigenin performs well to add to current treatment in ccRCC and confirm the value to target EGFR to improve therapy in RCC.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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