Abstract
Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-o-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.
Highlights
Introduction conditions of the Creative CommonsSkin squamous cell carcinoma (SSCC) is the second most prevalent of all human cancers worldwide [1]
We evaluated if the topical administration of the AgNMS complex loaded in a transdermal device based on bacterial cellulose membrane (BCM), named AgMNS@BCM, in male Balb/c mice would bring local and/or systemic adverse effects as well as its efficacy in vivo studies in mice with induced
The peak-by-peak comparison of the IR spectra of AgNMS@BCM with the free AgNMS and BCM showed that in the region < 2000 cm−1 all the peaks correspond to the unshifted vibrations observed for the precursor materials
Summary
Introduction conditions of the Creative CommonsSkin squamous cell carcinoma (SSCC) is the second most prevalent of all human cancers worldwide [1]. The tumor originates in keratinocytes of the basal extract of the epidermis and occurs in areas exposed to the sun, such as ears, face, scalp, and neck [2]. Pharmaceutics 2022, 14, 462 radiation is the main cause of SSCC. UV radiation of the sun can directly modify the DNA structure of keratinocytes by formation of cyclobutanepyrimidine dimers and pyrimidinepyrimidone photoproducts or indirectly by formation of reactive oxygen species (ROS) [3,4,5], leading to the emergence of SSCC as a consequence. UV radiation can act on initiation, promotion, and progression of SSCC indirectly by the induction of inflammation, where the cyclooxygenase-2 (COX-2) protein has unequivocal importance [6,7,8,9,10,11,12]
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