Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics
Issued Date
2022-06-01
Resource Type
eISSN
20763921
Scopus ID
2-s2.0-85131583206
Journal Title
Antioxidants
Volume
11
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antioxidants Vol.11 No.6 (2022)
Suggested Citation
Nelson D.R., Al Hrout A., Alzahmi A.S., Chaiboonchoe A., Amin A., Salehi-Ashtiani K. Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics. Antioxidants Vol.11 No.6 (2022). doi:10.3390/antiox11061125 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83219
Title
Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics
Other Contributor(s)
Abstract
The spice saffron (Crocus sativus) has anticancer activity in several human tissues, but the molecular mechanisms underlying its potential therapeutic effects are poorly understood. We investigated the impact of safranal, a small molecule secondary metabolite from saffron, on the HCC cell line HepG2 using untargeted metabolomics (HPLC–MS) and transcriptomics (RNAseq). Increases in glutathione disulfide and other biomarkers for oxidative damage contrasted with lower levels of the antioxidants biliverdin IX (139-fold decrease, p = 5.3 × 105), the ubiquinol precursor 3-4-dihydroxy-5-all-trans-decaprenylbenzoate (3-fold decrease, p = 1.9 × 10−5), and resolvin E1 (−3282-fold decrease, p = 45), which indicates sensitization to reactive oxygen species. We observed a significant increase in intracellular hypoxanthine (538-fold increase, p = 7.7 × 10−6) that may be primarily responsible for oxidative damage in HCC after safranal treatment. The accumulation of free fatty acids and other biomarkers, such as S-methyl-5′-thioadenosine, are consistent with safranal-induced mitochondrial de-uncoupling and explains the sharp increase in hypoxanthine we observed. Overall, the dual omics datasets describe routes to widespread protein destabilization and DNA damage from safranal-induced oxidative stress in HCC cells.