Human Skin Cancer Research Articles

The Carcinogenesis of the Human Scalp: An Immunometabolic-Centered View

The human scalp is a common site of skin cancer in humans, with nonmelanoma skin cancer being exceedingly common. In this review, two dermatologists with extensive experience in cutaneous oncology will discuss unique features of the epidemiology of cancer of the scalp. Clinical observations on these common skin cancers lead to insight into the pathogenesis and potential prevention and treatment of cutaneous scalp neoplasia. Our hypothesis is that the presence of hair protects against the development of skin cancer but not by serving as a physical shield but rather by providing continuous IL-17-biased immunosurveillance. The loss of hair allows for a release from immunosurveillance, resulting in the expansion of neoplastic cells towards skin cancer. Both hair follicles and metabolic changes in stroma allow for permissiveness for tumor promotion.

Characterization of Human Melanoma Skin Cancer Models: A step towards Model-Based Melanoma Research.

Advancing 3D in vitro human tissue models is crucial for biomedical research and drug development to address the ethical and biological limitations of animal testing. Recently, 3D skin models have proven to be effective for studying serious skin conditions, such as melanoma. For these advanced models to be applicable in preclinical studies, thorough characterization is essential to understand their applicability and limitations. In this study, we used bioimaging and RNA sequencing to assess the architecture and transcriptomic profiles of skin models, including models with melanoma. Our results indicated that these models closely mimicked skin morphology and gene expression patterns. The full-thickness (FT) model shows a superior resemblance to the human skin, particularly in basement membrane formation and cellular interactions. The integrity of the skin-like properties and gene expression signatures of both skin and melanoma cells were preserved upon the integration of melanoma cells, establishing these models as robust platforms for cancer research. The responsiveness of the FT melanoma models to vemurafenib treatment was successfully monitored, demonstrating their validity as a reliable, reproducible, and humane tool for pharmacological testing and drug development. Furthermore, the transcriptomic data showed that skin models with cancer spheroids had upregulated genes linked to aggressive and resilient cancer behavior compared to spheroids alone. This emphasizes the importance of the microenvironment in cancer progression and suggests that 3D skin models can serve to uncover mechanisms and therapeutic targets that are not detectable in simpler systems. STATEMENT OF SIGNIFICANCE: This study introduces advanced, ethically sound skin and melanoma models as alternatives to animal testing in drug discovery. By thoroughly characterizing these models using bioimaging and RNA sequencing, we demonstrate their close resemblance to human skin, particularly in full-thickness models. These models not only replicate the complex cellular interactions and gene expression patterns of human tissue but also maintain robustness after melanoma integration. Our findings highlight the potential of these models in revealing cancer mechanisms and therapeutic targets, offering a significant impact on melanoma research and preclinical testing.

Disabled 2 (Dab2) Regulates Tumour Progression in Skin Squamous Cell Carcinoma.

Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression. We generated tamoxifen inducible Dab2 conditional knockout system for our study. Loss of Dab2 led to delayed papilloma initiation and reduced papilloma burden. Delayed papilloma initiation was due to reduce proliferative potential of the papillomas due to Dab2 loss. Furthermore, while the WT papillomas progressed to SCC, the papillomas formed in Dab2 cKO mice failed to undergo malignant conversion to SCC. Dab2 cKO tumours showed reduced expression of K8, a marker for aggressive tumour. Moreover, Dab2 ckO tumours failed to undergo EMT as shown by reduced expression of Vimentin and Twist1. Dab2 cKO tumours also showed reduced expression of Sox2, a stem cell marker. Furthermore, qPCR analysis showed upregulation of Dab2 expression in the human skin cancer cell lines as compared to normal human skin keratinocytes. In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.

P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway.

Our previous research has demonstrated that P2RY6 functions as an oncogene in DMBA/TPA-induced two-stage chemical skin carcinogenesis in mice. However, considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we found that P2ry6-deficient mice exhibited marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, a P2ry6 gene knockout promoted skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, could inhibit the short-term UVB-induced increase of epiderma thickness in mouse skin. Furthermore, UVB irradiation could significantly upregulate P2RY6 expression in human and mouse skin cells. These results indicated that P2RY6 may play a crucial protective role in resisting the UVB-induced formation of skin tumors. At the molecular level, the loss of the P2RY6 gene inhibits the ubiquitination modification and expression of XPC after UVB irradiation in skin keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). We have also demonstrated that P2RY6 deletion activates the PI3K/AKT signaling pathway both invitro and invivo. The CPD accumulation and acute inflammatory response enhanced by the loss of the P2RY6 gene can be reversed by an AKT inhibitor. These findings suggest that P2RY6 may act as a tumor suppressor in UVB-induced skin cancer by regulating the PI3K/AKT signaling pathway.

Synthesis of chitosan/Fe2O3/CuO-nanocomposite and their role as inhibitor for some biological disorders in vitro with molecular docking interactions studies

The hybrid material between the functional elements particularly with the polymer compounds as a nanocomposites are attractive in numerous fields. In the current work, chitosan/Fe2O3/CuO-nanocomposite has been successfully synthesized in situ via a coprecipitation method and characterized by several apparatuses. The X-ray diffraction cleared that chitosan/Fe2O3/CuO-nanocomposite was crystalline. Transmission Electron Microscopy (TEM) showed that the size of chitosan/Fe2O3/CuO-nanocomposite was of 17–85 nm. Candida albicans, Candida tropicalis, and Geotrichum candidum were inhibited employing the chitosan/Fe2O3/CuO-nanocomposite with inhibition areas of 25 ± 0.1 and 30 ± 0.1, and 23 ± 0.2 mm, respectively. Minimum inhibitory concentration (MIC) of chitosan/Fe2O3/CuO-nanocomposite was 15.62, 31.25, and 62.5 μg/mL for C. tropicalis, C. albicans, and G. candidum, respectively. Biofilm formation of C. albicans, C. tropicalis and G. candidum was inhibited at level of 95.31, 96.65, and 93.63 %, respectively at 75 % MIC of chitosan/Fe2O3/CuO-nanocomposite. The exposed C. tropicalis to chitosan/Fe2O3/CuO-nanocomposite showed severe damag of cytoplasm membrane with cell wall rupture. Chitosan/Fe2O3/CuO-nanocomposite reflected anticancer potential against human skin cancer (A-431) cells with IC50 of 77.79 ± 1.37 μg/mL. Moreover, wound heals was induced by chitosan/Fe2O3/CuO-nanocomposite with closure level 92.76 %. Molecular docking studies suggested strong binding of C. tropicalis (PDB ID: 8BH8) and A-431 (PDB ID: 5JJX) proteins with CuO nanoparticles and FeO nanoparticles.

Cover Feature: Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells (Chem. Eur. J. 48/2024)

Cover Feature: Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells (Chem. Eur. J. 48/2024)

Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks.

Characterizing the transcriptional and translational gene expression patterns at the single-cell level within their three-dimensional (3D) tissue context is essential for revealing how genes shape tissue structure and function in health and disease. However, most existing spatial profiling techniques are limited to 5-20 μm thin tissue sections. Here, we developed Deep-STARmap and Deep-RIBOmap, which enable 3D in situ quantification of thousands of gene transcripts and their corresponding translation activities, respectively, within 200-μm thick tissue blocks. This is achieved through scalable probe synthesis, hydrogel embedding with efficient probe anchoring, and robust cDNA crosslinking. We first utilized Deep-STARmap in combination with multicolor fluorescent protein imaging for simultaneous molecular cell typing and 3D neuron morphology tracing in the mouse brain. We also demonstrate that 3D spatial profiling facilitates comprehensive and quantitative analysis of tumor-immune interactions in human skin cancer.

Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells.

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-β-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.

Assessment of luminescent copper nanomaterials as anti-germs, anti-proliferation efficiencies using green nano-strategy.

For the first time, we suggest using leaf extract from Ocimum americanum as the economically viable bio-fabrication of copper nanomaterials. The residuals of leaf extract bio-capping provide the stability of the nanomaterials in-situ. UV-Vis and XRD confirmed the formation, with the UV-Vis spectrum of Cu-NMs revealing a surface plasmon resonance characteristic peak at 350 nm. FT-IR analysis was employed to examine the functional groups. FE-SEM with EDX was used to assess the morphology and carry out an elemental analysis of the nanomaterials. Diffusion and MTT assays were used to study the antimicrobial and anticancer activities. The synthesized copper nanomaterials exhibited in-vitro cytotoxicity against human skin cancer (A431) cell lines. Green nanomaterial was examined against the methylene blue dye, photodegradation was reduced by up to 90.6% within 50 minutes. The copper nanomaterials synthesized in our study exhibit promising applications in biomedicine and environmental pollution research.

Combination of Muller matrix imaging polarimetry and artificial intelligence for classification of mice skin cancer tissue in-vitro and in-vivo

Mueller matrix imaging polarimetry is a fast and non-invasive technique for discriminating between different types of biological samples based on the characteristics of polarized light interacting with them. Combining Mueller matrix imaging polarimetry with artificial intelligence provides further advantages in detecting different kinds of medical conditions in an automated manner. Accordingly, the present study proposes a method based on Mueller matrix polarimetry and machine learning algorithms for discriminating between (1) four different types of mice skin tissues (normal, acanthosis, papilloma, and squamous cell carcinoma); (2) two types of mice skin tissues which show histological similarities to human equivalents (normal and squamous cell carcinoma); and (3) 7,12-dimethylbenz[a]anthracene/estrogen-induced mice skin tissues. Five machine learning classifiers, namely Random Forest, Support Vector Machine, K-Nearest Neighbor, Gradient Boosting, and Gaussian Naïve Bayes, are considered in the first and second applications, while three models (Support Vector Machine, K-Nearest Neighbor, Gradient Boosting) are considered in the third application. For each application, the features which dominate the machine learning prediction performance are determined through multivariate correlation matrix analysis, kernel density estimation, and Analysis of Variance tests. The experimental results show that the Random Forest model achieves the highest classification accuracy (93.55 %) for the first application, while the Support Vector Machine model yields the highest accuracy for both the second and third applications (97.66 % and 100 %, respectively). Overall, the proposed framework consisting of Mueller matrix imaging polarimetry and machine learning provides a strong foundation for the on-going development of screening and diagnosis methods for human skin cancer.

Determination of flavonoid content in Grammatophyllum speciosum and in vitro evaluation of their anti-skin cancer and antibacterial activities

Grammatophyllum speciosum Blume, a plant of significant pharmacological and cultural importance in its native regions, has been the subject of traditional medicinal use. This study, however, delves deeper into the unique attributes of G. speciosum aerial part and root extracts, particularly their phytochemical content, antioxidant potential, antibacterial activity, and anticancer properties against human skin cancer cells. The results unveiled a promising aspect-higher flavonoid and phenolic compound levels in the aerial part compared to the root extracts. Both aerial part and root extracts demonstrated significant antioxidant activities, as evidenced by their ability to scavenge DPPH radicals and reduce ferric ions in the FRAP assay. Moreover, the ethanolic extract derived from G. speciosum aerial parts showed promising antibacterial activity against both gram-positive and gram-negative bacteria, hinting at its potential therapeutic efficacy. Notably, this extract also demonstrates a capacity to impede the viability of human skin cancer cells (A375). Collectively, these results demonstrated the potential applications of the G. speciosum aerial part extracts. Further investigation is imperative to elucidate the intricate molecular mechanisms underpinning these diverse effects, thereby contributing to a deeper understanding of the pharmacological potential of G. speciosum and its prospective applications in medicine and beyond.

Synthesis and structural evaluation of (5-(6-(Furan-2-ylmethylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl Dihydrogen Phosphate as a Redox Drug Discovery Targeting Human Skin Cancer

Synthesis and structural evaluation of (5-(6-(Furan-2-ylmethylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl Dihydrogen Phosphate as a Redox Drug Discovery Targeting Human Skin Cancer

Comparative Study of the Potential Cell-Penetrating Peptide ∆M4 on Apoptosis Cell Signaling in A375 and A431 Cancer Cell Lines.

In recent yearsjajajj, peptide-based therapeutics have attracted increasing interest as a potential approach to cancer treatment. Peptides are characterized by high specificity and low cytotoxicity, but they cannot be considered universal drugs for all types of cancer. Of the numerous anticancer-reported peptides, both natural and synthetic, only a few have reached clinical applications. However, in most cases, the mechanism behind the anticancer activity of the peptide is not fully understood. For this reason, in this work, we investigated the effect of the novel peptide ∆M4, which has documented anticancer activity, on two human skin cancer cell lines. A novel approach to studying the potential induction of apoptosis by anticancer peptides is the use of protein microarrays. The results of the apoptosis protein study demonstrated that both cell types, skin malignant melanoma (A375) and epidermoid carcinoma (A431), exhibited markers associated with apoptosis and cellular response to oxidative stress. Additionally, ∆M4 induced concentration- and time-dependent moderate ROS production, triggering a defensive response from the cells, which showed decreased activation of cytoplasmic superoxide dismutase. However, the studied cells exhibited a differential response in catalase activity, with A375 cells showing greater resistance to the peptide action, possibly mediated by the Nrf2 pathway. Nevertheless, both cell types showed moderate activity of caspases 3/7, suggesting that they may undergo partial apoptosis, although another pathway of programmed death cannot be excluded. Extended analysis of the mechanisms of action of anticancer peptides may help determine their effectiveness in overcoming chemoresistance in cancerous cells.

Effective prediction of human skin cancer using stacking based ensemble deep learning algorithm

ABSTRACT Automated diagnosis of cancer from skin lesion data has been the focus of numerous research. Despite that it can be challenging to interpret these images because of features like colour illumination changes, variation in the sizes and forms of the lesions. To tackle these problems, the proposed model develops an ensemble of deep learning techniques for skin cancer diagnosis. Initially, skin imaging data are collected and preprocessed using resizing and anisotropic diffusion to enhance the quality of the image. Preprocessed images are fed into the Fuzzy-C-Means clustering technique to segment the region of diseases. Stacking-based ensemble deep learning approach is used for classification and the LSTM acts as a meta-classifier. Deep Neural Network (DNN) and Convolutional Neural Network (CNN) are used as input for LSTM. This segmented images are utilized to be input into the CNN, and the local binary pattern (LBP) technique is employed to extract DNN features from the segments of the image. The output from these two classifiers will be fed into the LSTM Meta classifier. This LSTM classifies the input data and predicts the skin cancer disease. The proposed approach had a greater accuracy of 97%. Hence, the developed model accurately predicts skin cancer disease.

Molecular mechanisms of human papilloma virus related skin cancers: A review.

The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV infections occur asymptomatically and resolve spontaneously. However, infection with high-risk viral strains can lead to the development of preneoplastic lesions, with an increased propensity to become cancerous. The location of these malignancies includes the oral cavity, cervix, vagina, anus, and vulva, among others. The role of HPV in carcinogenesis has already been demonstrated for the aforementioned neoplasia. However, regarding skin malignancies, the mechanisms that pinpoint the role played by HPV in their initiation and progression still elude our sight. Until now, the only fully understood mechanism of viral cutaneous oncogenesis is that of human herpes virus 8 infection in Kaposi sarcoma. In the case of HPV infection, however, most data focus on the role that beta strains exhibit in the oncogenesis of cutaneous squamous cell carcinoma (cSCC), along with ultraviolet radiation (UVR) and other environmental or genetic factors. However, recent epidemiological investigations have highlighted that HPV could also trigger the onset of other non-melanocytic, for example, basal cell carcinoma (BCC), and/or melanocytic skin cancers, for example, melanoma. Herein, we provide an overview of the role played by HPV in benign and malignant skin lesions with a particular focus on the main epidemiological, pathophysiological, and molecular aspects delineating the involvement of HPV in skin cancers.

Alginate Nanoparticles Containing Cuminum cyminum and Zataria multiflora Essential Oils with Promising Anticancer and Antibacterial Effects.

Cancer and bacterial infections are major global health concerns driving the need for innovative medicines. This study investigated alginate nanoparticles loaded with essential oils (EOs) from Cuminum cyminum and Zataria multiflora as potential drug delivery systems. The nanoparticles were comprehensively characterized using techniques such as gas chromatography-mass spectrometry (GC-MS), dynamic light scattering (DLS), zetasizer, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Their biological properties against two human skin cancer cell lines (A-375 and A-431) and three bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) were also evaluated. Alginate nanoparticles containing C. cyminum and Z. multiflora EOs exhibited sizes of 160 ± 8 nm and 151 ± 10 nm, respectively. Their zeta potentials and encapsulation efficiencies were -18 ± 1 mV and 79 ± 4%, as well as -27 ± 2 mV and 86 ± 5%, respectively. The IC50 values against the tested cell lines and bacteria revealed superior efficacy for nanoparticles containing Z. multiflora EO. Considering the proper efficacy of the proposed nanoparticles, the straightforward preparation method and low cost suggest their potential for further in vivo studies.

White horses - non-coding sequences drive premature hair greying and predisposition to melanoma.

The Grey allele in horses is causing premature hair greying and susceptibility to melanoma. The causal mutation is a 4.6 kb tandem duplication in intron 6 of the Syntaxin 17 gene. A recent study demonstrated that the most common allele at the Grey locus (G3) involves three tandem copies of this sequence, whilst a more rare allele (G2) has two tandem copies and the wild-type allele (G1) only one copy. The G3 allele is causing fast greying and high incidence of skin melanoma, whereas the G2 allele is causing slow greying and no obvious increase in melanoma incidence. Further somatic copy number expansion has been documented in melanoma tissue from Grey horses. Functional studies showed that this intronic sequence acts as a weak melanocyte-specific enhancer that becomes substantially stronger by the copy number expansion. The Grey mutation is associated with upregulated expression of both Syntaxin 17 and the neighbouring NR4A3 gene in Grey horse melanomas. It is still an open question which of these genes is most important for the phenotypic effects or if causality is due to the combined effect of upregulation of both genes. Interestingly, RNAseq data in the Human Protein Atlas give support for a possible role of NR4A3 because it is particularly upregulated in human skin cancer, and it belongs to a cluster of genes associated with skin cancer and melanin biosynthesis. The Grey mutation and its association with melanoma provide a possibility to study the path to tumour development in numerous Grey horses carrying exactly the same predisposing mutation.

An Extensive Investigation into the Use of Machine Learning Tools and Deep Neural Networks for the Recognition of Skin Cancer: Challenges, Future Directions, and a Comprehensive Review

Skin cancer poses a serious risk to one’s health and can only be effectively treated with early detection. Early identification is critical since skin cancer has a higher fatality rate, and it expands gradually to different areas of the body. The rapid growth of automated diagnosis frameworks has led to the combination of diverse machine learning, deep learning, and computer vision algorithms for detecting clinical samples and atypical skin lesion specimens. Automated methods for recognizing skin cancer that use deep learning techniques are discussed in this article: convolutional neural networks, and, in general, artificial neural networks. The recognition of symmetries is a key point in dealing with the skin cancer image datasets; hence, in developing the appropriate architecture of neural networks, as it can improve the performance and release capacities of the network. The current study emphasizes the need for an automated method to identify skin lesions to reduce the amount of time and effort required for the diagnostic process, as well as the novel aspect of using algorithms based on deep learning for skin lesion detection. The analysis concludes with underlying research directions for the future, which will assist in better addressing the difficulties encountered in human skin cancer recognition. By highlighting the drawbacks and advantages of prior techniques, the authors hope to establish a standard for future analysis in the domain of human skin lesion diagnostics.

The Surprising Diversity of UV‐Induced Mutations

AbstractUltraviolet (UV) light is the most pervasive environmental mutagen and the primary cause of skin cancer. Genome sequencing of melanomas and other skin cancers has revealed that the vast majority of somatic mutations in these tumors are cytosine‐to‐thymine (C>T) substitutions in dipyrimidine sequences, which, together with tandem CC>TT substitutions, comprise the canonical UV mutation “signature”. These mutation classes are caused by DNA damage directly induced by UV absorption, namely cyclobutane pyrimidine dimers (CPDs) or 6‐4 pyrimidine‐pyrimidone photoproducts (6‐4PP), which form between neighboring pyrimidine bases. However, many of the key driver mutations in melanoma do not fit this mutation signature, but instead are caused by T>A, T>C, C>A, or AC>TT substitutions, frequently occurring in non‐dipyrimidine sequence contexts. This article describes recent studies indicating that UV light causes a more diverse spectrum of mutations than previously appreciated, including many of the mutation classes observed in melanoma driver mutations. Potential mechanisms for these diverse mutation signatures are discussed, including UV‐induced pyrimidine‐purine photoproducts and indirect DNA damage induced by UVA light. Finally, the article reviews recent findings indicating that human DNA polymerase eta normally suppresses these non‐canonical UV mutation classes, which can potentially explain why canonical C>T substitutions predominate in human skin cancers.

Production and characterization of melanin pigment from black fungus Curvularia soli AS21 ON076460 assisted gamma rays for promising medical uses

Owing to the growing need for natural materials in different fields, studying melanin production from biological sources is imperative. In the current study, the extracellular melanin pigment was produced by the fungus Curvularia soli AS21 ON076460. The factors that affect the production of melanin were optimized by the Plackett-Burman design (P-BD). The effect of gamma irradiation on melanin productivity was investigated. The maximum melanin yield (3.376 mg/L) was elicited by a stimulus of gamma irradiation at 1.0 kGy. The results evoked that, Curvularia soli AS21 ON076460 melanin exhibited excellent antimicrobial activity against all tested bacteria and fungi. Klebsiella pneumoniae ATCC 13883 and P. digitatum were mostly affected by melanin registering the inhibition zone diameters of 37.51 ± 0.012 and 44.25 ± 0.214 mm, respectively. Moreover, Curvularia soli AS21 ON076460 melanin indicated a significant antiviral efficacy (77% inhibition) of Herpes simplex virus (HSV1). The melanin pigment showed antioxidant activities with IC50 of 42 ± 0.021 and 17 ± 0.02 µg/mL against DPPH and NO, respectively. Melanin had cytotoxic action against human breast cancer and skin cancer cell lines (Mcf7and A431) as well as exerting a low percentage of cell death against normal skin cell lines (Hfb4). Melanin was effective in wound management of human skin cells by 63.04 ± 1.83% compared with control (68.67 ± 1.10%). The novelty in the study is attributed to the possibility of using gamma rays as a safe method in small economic doses to stimulate melanin production from the fungi that have been isolated. In summary, melanin produced from fungi has significant biological activities that encourage its usage as a supportive medical route.