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Updated: Feb 2, 2026

Live-Cell Imaging of Transcriptional Activity at DNA Double-Strand Breaks
Published on: September 20, 2021
Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells
Ala'a Al-Hrout1, Amphun Chaiboonchoe2, Basel Khraiwesh2,3
1Biology Department, College of Science, UAE University, P.O. Box 15551, Al-Ain, UAE.
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.
Insights
Safranal, a compound from saffron, shows promise as an anticancer therapy for hepatocellular carcinoma (HCC). It induces cancer cell death by triggering endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) presents poor prognoses, necessitating novel therapeutic strategies.
- Alternative treatments are crucial for effective HCC management and improved patient outcomes.
Purpose of the Study:
- To investigate the anticancer effects of safranal on hepatocellular carcinoma (HCC) cells.
- To elucidate the molecular mechanisms underlying safranal's anti-HCC activity, including its impact on cell cycle, DNA damage, and apoptosis.
Main Methods:
- In vitro cell-based assays (cell cycle, immunoblotting, apoptosis assays).
- In silico analyses and network analysis.
- Gene set enrichment analysis (GSEA) to identify affected pathways.
Main Results:
- Safranal induced distinct cell cycle arrest at G2/M and S phases.
- Safranal demonstrated a pro-apoptotic effect via activation of caspases, indicating ER stress-mediated apoptosis.
- Gene set enrichment analysis revealed upregulation of the unfolded protein response (UPR) pathway.
Conclusions:
- Safranal exhibits significant anticancer effects against HCC cells.
- Safranal-induced apoptosis is mediated through endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).
- Safranal represents a potential therapeutic candidate for HCC treatment.
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