Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

Feehan, Robert P.; Shantz, Lisa M.

doi:10.1042/bcj20160471

Cited by 44 publications

(54 citation statements)

References 222 publications

(255 reference statements)

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“…Non-Melanoma Skin Cancer, abbreviated NMSC, is the most commonly diagnosed disease and is a significant health concern in terms of incidence rate and economic health care costs [1], [2]. According to the American Cancer Society, approximately 3.3 million Americans are diagnosed with NMSC each year [5].…”

Section: Non-melanoma Skin Cancermentioning

confidence: 99%

“…NMSC takes two main forms -Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC). BCC occurs most frequently in the human population, representing approximately 80% of all NMSCs [2], [5]. BCC and SCC originate in the basal and squamous cell layers respectively.…”

Section: Non-melanoma Skin Cancermentioning

confidence: 99%

“…Ultra Violet Radiation (UVR) is a detrimental exogenous agent responsible for genome damage in all species [4]. In general, UV light is composed of three separate types differentiated by their respective wavelengths: UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm) [2]. UVA lies closest to the visible light spectrum (700-400nm) on a scale of increasing wavelength ( Figure 5).…”

Section: Uv Lightmentioning

confidence: 99%

“…Non-Melanoma Skin Cancer (NMSC) affects approximately 3.3 million Americans each year and is currently the most commonly diagnosed disease [1], [2], [5]. The common forms of NMSC are Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC), with BCC representing about 80% of NMSCs [2], [17] Given the prevalence of NMSC in the human population, understanding the cause and potential treatments is crucial.…”

Section: Introductionmentioning

confidence: 99%

“…However, the fate of the fluorescent probe is unknown. In this current experiment, cells were introduced to FSM for 1 hour or 24 hour continuous incubations, FSM was removed, media was exchanged, and cells were immediately subjected to 40 mJ/cm2 of UVB radiation. Cells were fixed 1 hour, 2 hour, 12 hour, and 24 hour post-UV.…”

mentioning

confidence: 99%

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Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Kandell¹

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Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes Rebecca Marie Kandell Non Melanoma Skin Cancer (NMSC) affects 3.3 million Americans each year and results from Ultra Violet Radiation (UVR) damage to DNA in the form of pyrimidine dimers and photoproducts [1]-[5]. Cells directly detect the damage and initiate apoptosis, cell cycle arrest, or DNA repair by modulating p53 and p21 levels [6]-[9]. Current methods of photoprotection include sunscreen, but controversy over safety of some active ingredients necessitates research into more natural alternatives [10]-[12]. In particular, 24 hour incubation with bovine milk sphingomyelin (BSM) has demonstrated photoprotective potential by reducing p21 and p53 levels in keratinocytes (KRTs) after UV radiation [13], [14]. This thesis aims to expand on past BSM research by exploring the mechanism for photoprotection. Normally, sphingomyelin (SM) is metabolically degraded to ceramide which then leads to cell apoptosis [6]. The goals of this thesis were to characterize a fluorescent SM (FSM) to assess changes in intracellular fluorescence distribution after various incubation and post-UV exposure times. FSM was deemed functionally equivalent to BSM by reducing levels of p21 after UV. Furthermore, quantification demonstrated that FSM trafficking and intracellular fluorescence were independent of continuous incubation time, warranting further investigation into shorter timepoints like 1 hour. Across several post-UV timepoints, the 1 hour incubation had a consistently higher average cytoplasmic mean gray value compared to 24 hour incubation. In addition, the no UV control was significantly lower compared to the 24 hour and 12 hour post-UV timepoints. No post-UV differences were observed for the 24hour incubation, suggesting future work is necessary for the 1 hour incubation, which potentially streamlines future experiments. Two immunofluorescence stains for endogenous SM (lysenin) and ceramide were also optimized for preliminary fluorescence distribution studies and v colocalization with FSM. Finally, a 3T3 fibroblast spheroid model was utilized as proof-ofconcept for future 3D KRT cultures and depth of dye penetration quantification methods. These findings suggest FSM is an appropriate model for BSM trafficking, a shorter FSM incubation time could potentially be adopted in future studies, dual immunofluorescence staining for SM and ceramide is viable, and spheroids provide a promising model for future 3D KRT studies.

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Section: Non-melanoma Skin Cancermentioning

confidence: 99%

Section: Non-melanoma Skin Cancermentioning

confidence: 99%

Section: Uv Lightmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Kandell¹

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Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review

Zamanian,

Shahbazi,

Kazmi

et al. 2024

Food Science & Nutrition

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Nonmelanoma skin cancer (NMSC) represents the most prevalent form of skin cancer globally, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common types. The search for effective chemopreventive and therapeutic agents has led to the exploration of natural compounds, among which resveratrol (RES), a polyphenolic phytoalexin found in grapes, berries, peanuts, and red wine, has garnered significant attention. This comprehensive review aims to elucidate the effects of RES on NMSC, focusing on its mechanisms of action, efficacy in preclinical studies, and potential as a chemopreventive and therapeutic agent. RES exhibits promising chemopreventive and antineoplastic capabilities against NMSC through various mechanisms, including the induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and anti‐inflammatory activities. Studies have demonstrated that RES can significantly enhance the effectiveness of traditional chemotherapeutic agents, such as 5‐fluorouracil (5‐FU), by inhibiting cellular proliferation and inducing apoptosis in cancerous cells. Furthermore, resveratrol's antioxidant properties may mitigate the impact of reactive oxygen species (ROS) triggered by UV exposure, thus reducing DNA damage and mutations associated with skin cancer development. In vitro and in vivo experiments have shown that RES can effectively hinder the growth and spread of various tumor cell types, including human cutaneous SCC A431 cells, and induce apoptosis. The development of advanced delivery systems, such as nanostructured lipid carriers and liposomes, has been recognized for their potential to enhance the therapeutic effects of RES, particularly its anticancer properties. In conclusion, RES presents a viable candidate for the prevention and treatment of NMSC, owing to its multifaceted mechanisms of action, including its ability to regulate oxidative stress, trigger apoptosis, and inhibit proliferation. However, further clinical studies are required to fully understand its effectiveness and safety in humans, as well as to optimize delivery methods for improved bioavailability and therapeutic outcomes.

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Skin cancer, including related pathways and therapy and the role of luteolin derivatives as potential therapeutics

Juszczak

Wölfle

Končić

2022

Medicinal Research Reviews

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Cutaneous malignant melanoma is the fastest growing and the most aggressive form of skin cancer that is diagnosed. However, its incidence is relatively scarce compared to the highest mortality rate of all skin cancers. The much more common skin cancers include nonmelanoma malignant skin cancers. Moreover, over the past several decades, the frequency of all skin cancers has increased much more dynamically than that of almost any other type of cancer. Among the available therapeutic options for skin cancers, chemotherapy used immediately after the surgical intervention has been an essential element. Unfortunately, the main problem with conventional chemopreventive regimens involves the lack of response to treatment and the associated side effects. Hence, there is a need for much more effective anticancer drugs. Correspondingly, the targeted alternatives have involved phytochemicals, which are safer chemotherapeutic agents and exhibit competitive anticancer activity with high therapeutic efficacy. Among polyphenolic compounds, some flavonoids and their derivatives, which are mostly found in medicinal plants, have been demonstrated to influence the modulation of signaling pathways at each stage of the carcinogenesis process, which is also important in the context of skin cancers. Hence, this review focuses on an exhaustive overview of the therapeutic effects of luteolin and its derivatives in the treatment and prevention of skin cancers. The bioavailability and structure–activity relationships of luteolin derivatives are also discussed. This review is the first such complete account of all of the scientific reports concerning this particular group of natural compounds that target a specific area of neoplastic diseases.

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Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

Cited by 44 publications

References 222 publications

Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Assessing the Photoprotective Effects of Fluorescent Sphingomyelin Against UVB Induced DNA Damage in Human Keratinocytes

Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review

Skin cancer, including related pathways and therapy and the role of luteolin derivatives as potential therapeutics

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