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TP53 downregulation in non-melanoma skin cancer cells treated with citrus limon (Cl) essential oil

Zamani, Muhammad Razin and Wan Omar, Wan Fatein Nabeila and Mohd. Radzuan, Hazulin and Anuar, Muhammad Ashraf Fithri and Muzamil, Muslihah (2026) TP53 downregulation in non-melanoma skin cancer cells treated with citrus limon (Cl) essential oil. Borneo Journal of Medical Sciences, 20 (3). pp. 380-390. ISSN 1985-1758 E-ISSN 2710-7353

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Abstract

Citrus limon essential oil (CLEO) is rich in bioactive compounds, exhibit various therapeutic properties, including anticancer potential. Non-melanoma skin cancers, such as squamous cell carcinoma, are commonly associated with TP53 mutations, leading to uncontrolled cell proliferation. This study investigates the cytotoxic effects of CLEO on normal human foreskin fibroblast cells (HFF1) and human squamous carcinoma cells (A431) by analysing morphological changes, p53 protein secretion, and TP53 gene expression. HFF1 and A431 cells were treated with CLEO at concentrations of 125, 250, and 500 µg/ mL for 24 hours. Morphological changes were observed using an inverted light microscope, while p53 protein secretion was analysed via Western blot. TP53 gene expression was assessed using quantitative real-time PCR. Mild structural changes were observed in HFF1 cells at higher CLEO concentrations (250 and 500 µg/mL), whereas A431 cells exhibited significant membrane blebbing and detachment at all concentrations (125, 250, and 500 µg/mL). p53 protein secretion in the culture media increased in HFF1 cells following CLEO treatment, while A431 cells exhibited a dose-dependent reduction in p53 secretion. Additionally, TP53 gene expression was notably downregulated in A431 cells at 125 and 500 µg/mL CLEO concentrations, suggesting the presence of alternative cytotoxic mechanisms. CLEO shows stronger cytotoxicity against A431 squamous carcinoma cells than against normal HFF1 fibroblasts, suggesting therapeutic potential. The modulation of p53 protein secretion and TP53 gene expression suggests that p53 operates through both dependent and independent mechanisms. Further studies, including in vivo and clinical investigations, are needed before its application in cancer therapy can be considered.

Item Type: Article (Journal)
Uncontrolled Keywords: Antineoplastic, natural products, skin neoplasms, phytogenic, antiproliferative
Subjects: Q Science > QP Physiology
R Medicine > RL Dermatology
R Medicine > RS Pharmacy and materia medica
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Medicine
Kulliyyah of Medicine > Department of Basic Medical
Depositing User: Dr Wan Fatein Nabeila Wan Omar
Date Deposited: 10 Sep 2026 16:05
Last Update: 10 Sep 2026 16:05
Queue Number: 2026-09-Q5037
URI: http://irep.iium.edu.my/id/eprint/131170
Indexed In: Google Scholar, MyCite

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