Pharmacological and In Vitro Studies on Quercetin-Rich Onion Peel Extract (Allium cepa) and N-Acetylcysteine Enhancing Apoptosis in Colorectal Cancer
DOI:
https://doi.org/10.48048/tis.2025.9111Keywords:
Onion peel extract, Quercetin, Genotoxicity, Pharmacological network, CRC, ApoptosisAbstract
Colorectal cancer (CRC) is one of the most common types of cancer globally with the second highest cancer-related mortality, having increased by almost 40 % over the past 40 years. Considering quercetin's limited bioavailability, N-acetylcysteine (NAC) has previously emerged as a promising candidate for treatment as it has been shown to stabilize quercetin and enhance its anti-cancer effectiveness. Therefore, the present study aims to investigate the effectiveness of onion peel extract and NAC in inducing apoptosis in CRC. Extracts were taken from onion peel using 60 % v/v ethanol and identified using High-Performance Liquid Chromatography (HPLC). Furthermore, the micronucleus assay was utilized to investigate the genotoxicity of the extract. Pharmacological network analysis was employed to elucidate the mechanism underlying the combined action of quercetin and NAC on CRC, with KEGG enrichment analysis also used to study key signaling pathways. Additionally, in vitro studies were conducted using MTT assay, apoptosis assay via flow cytometry, and western blot analysis in HT-29 and HCT-116 cells. Quercetin is a major compound in onion peel extract and showed no genotoxic effects. Pharmacological network analysis identified potential targets for quercetin and NAC combination therapy, revealing 363 overlapping target genes of quercetin and NAC in CRC, indicating their involvement in inducing CRC apoptosis. The KEGG pathway analysis revealed the top 10 pathways and showed that a majority of the genes were involved in MAPK pathways. In vitro studies demonstrated that the combined treatment significantly increased cytotoxicity and apoptosis induction, evidenced by upregulated expression of caspases 3, 7, 8, and 9 in HT-29 and HCT-116 cells. These findings emphasize the therapeutic potential of quercetin-rich onion peel extraction, characterized by the absence of genotoxicity, when used in combination with NAC therapy to enhance apoptosis efficacy in CRC. This approach holds promise as a candidate for alternative medicine in the treatment of human CRC.
HIGHLIGHTS
- Quercetin is a major compound in onion peel extract and showed no genotoxic effects using the micronucleus assay.
- Network pharmacology revealed that quercetin and NAC significantly modulate ROS-related genes and apoptotic pathways in CRC.
- Quercetin-rich extract and NAC together substantially activate caspases 3, 7, 8, and 9 in the apoptotic pathway of CRC cells.
GRAPHICAL ABSTRACT
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