Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells.

Background Hedgehog signaling pathway (Hh) is abnormally stimulated in colon cancer. Evidence suggests the therapeutic effectiveness of andrographolide against several cancers. This study attempts to delineate the effect of andrographolide on Hh signaling pathway in colon cancer HCT-116 cells. Metho...

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Publicado en:Nutrition & Cancer Vol. 73; no. 11/12; pp. 2428 - 2447
Autores principales: Khan, Imran, Mahfooz, Sadaf, Faisal, Mohammad, Alatar, Abdulrahman A., Ansari, Irfan A.
Formato: pictorial research tables/charts Journal Article
Publicado: Taylor & Francis Ltd 2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2021
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      pub: Taylor & Francis Ltd
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        10.1080/01635581.2020.1828942
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        atl: Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells.
      aug:
        au:
          Khan, Imran
          Mahfooz, Sadaf
          Faisal, Mohammad
          Alatar, Abdulrahman A.
          Ansari, Irfan A.
        affil: Department of Molecular Biology, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkey
      sug:
        subj:
          Plant Extracts Therapeutic Use
          Apoptosis
          Cell Cycle Drug Effects
          Colonic Neoplasms Drug Therapy
          Signal Transduction
          Cell Line
          Cytotoxicity Tests, Immunologic
          Cell Migration Assays Methods
          Staining and Labeling
          Cell Cycle Physiology
          Gene Expression
          Flow Cytometry
      ab: Background Hedgehog signaling pathway (Hh) is abnormally stimulated in colon cancer. Evidence suggests the therapeutic effectiveness of andrographolide against several cancers. This study attempts to delineate the effect of andrographolide on Hh signaling pathway in colon cancer HCT-116 cells. Methods: Effects of andrographolide were studied on HCT-116 cells by evaluating cytotoxicity by MTT assay, morphology assessment, trypan blue exclusion, and colony formation assay; migratory potential by scratch assay; apoptosis by DAPI, Hoechst staining, FITC-Annexin V assay, and caspases activation; mitochondrial membrane potential (ΔΨm) by Mito Tracker and Rhodamine 123. Intracellular ROS by DCFH-DA staining. Cell cycle regulation by flow cytometry. Expression of BAX, BAD, BCL2, Cyclin B1, CDK1, Smo, and Gli1 by qRT-PCR. Interaction between andrographolide and Smo protein by in-silico molecular docking. Results: Andrographolide induced antiproliferative effect on HCT-116 cells in a dose-dependent and time-dependent manner. It also induced apoptosis and anti-migratory effect in HCT-116 cells. In combination with 5FU, andrographolide exhibited synergistic effect. It Induced G2/M phase arrest through downregulating CDK1 and Cyclin B1. Andrographolide also inhibited Hh signaling by downregulating Smo and Gli1 in HCT-116 cells. It showed high affinity toward Smo protein in-silico. Conclusion: Andrographolide repressed the colon cancer cell growth via inhibiting Hh signaling pathway.
      pubtype: Academic Journal
      doctype:
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        research
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      ougenre: Article
    language: English
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