Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells

Ala'a Al-Hrout, Amphun Chaiboonchoe, Basel Khraiwesh, Chandraprabha Murali, Badriya Baig, Raafat El-Awady, Hamadeh Tarazi, Amnah Alzahmi, David Nelson, Yaser E. Greish, Wafaa Ramadan, Kourosh Salehi-Ashtiani, Amr Amin

    Research output: Contribution to journalArticle

    Abstract

    Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.

    Original languageEnglish (US)
    Number of pages1
    JournalScientific Reports
    Volume8
    Issue number1
    DOIs
    StatePublished - Nov 16 2018

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    Hepatocellular Carcinoma
    Cell Death
    DNA
    DNA Damage
    Cell Cycle
    Initiator Caspases
    Apoptosis
    G2 Phase
    Hep G2 Cells
    Cell Cycle Checkpoints
    S Phase
    DNA Repair
    Cell Division
    Computer Simulation
    Genes
    safranal
    Therapeutics
    Proteins

    ASJC Scopus subject areas

    • General

    Cite this

    Al-Hrout, A., Chaiboonchoe, A., Khraiwesh, B., Murali, C., Baig, B., El-Awady, R., ... Amin, A. (2018). Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-34855-0

    Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. / Al-Hrout, Ala'a; Chaiboonchoe, Amphun; Khraiwesh, Basel; Murali, Chandraprabha; Baig, Badriya; El-Awady, Raafat; Tarazi, Hamadeh; Alzahmi, Amnah; Nelson, David; Greish, Yaser E.; Ramadan, Wafaa; Salehi-Ashtiani, Kourosh; Amin, Amr.

    In: Scientific Reports, Vol. 8, No. 1, 16.11.2018.

    Research output: Contribution to journalArticle

    Al-Hrout, A, Chaiboonchoe, A, Khraiwesh, B, Murali, C, Baig, B, El-Awady, R, Tarazi, H, Alzahmi, A, Nelson, D, Greish, YE, Ramadan, W, Salehi-Ashtiani, K & Amin, A 2018, 'Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells', Scientific Reports, vol. 8, no. 1. https://doi.org/10.1038/s41598-018-34855-0
    Al-Hrout, Ala'a ; Chaiboonchoe, Amphun ; Khraiwesh, Basel ; Murali, Chandraprabha ; Baig, Badriya ; El-Awady, Raafat ; Tarazi, Hamadeh ; Alzahmi, Amnah ; Nelson, David ; Greish, Yaser E. ; Ramadan, Wafaa ; Salehi-Ashtiani, Kourosh ; Amin, Amr. / Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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