Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.
Saurabh SinghSarika YadavCeline CavalloDurgesh MouryaIshu SinghVijay KumarSachin ShuklaPallavi ShuklaRomil ChaudharyGyan Prakash MauryaRonja Lea Jennifer MüllerLilly RohdeAradhana MishraOlaf WolkenhauerShailendra GuptaAnurag TripathiPublished in: NPJ systems biology and applications (2024)
Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3β, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.
Keyphrases
- oxidative stress
- diabetic rats
- dna damage
- induced apoptosis
- skin cancer
- hydrogen peroxide
- reactive oxygen species
- wound healing
- soft tissue
- high glucose
- ischemia reperfusion injury
- anti inflammatory
- nitric oxide
- small cell lung cancer
- cell cycle arrest
- risk factors
- cell death
- tyrosine kinase
- heavy metals
- endothelial cells
- endoplasmic reticulum stress
- big data
- climate change
- artificial intelligence
- molecular docking
- machine learning
- genome wide
- single cell
- dengue virus
- gene expression
- deep learning
- protein protein
- life cycle
- preterm birth
- single molecule