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.

Platinum(II) and palladium(II) complexes have been investigated as potential anticancer drugs since the serendipitous discovery of the antineoplastic activities of cisplatin in the 1960s. Skin cancer is considered the most common malignant neoplasm that affects humans, and melanoma is the most lethal type of skin cancer. Surgical excision is the main form of treatment, which also may include radiotherapy, systemic chemotherapy, and immunotherapy. In this work, new insights concerning the structural characterization and in vitro anti-proliferative activity of the palladium(II) complex with the amino acid deoxyalliin (Pd-sac) against a panel of thirteen human tumor cells, with emphasis on skin cancer cell lines, are presented. The composition of the complex was confirmed by elemental analysis as [Pd(C₆H₁₀NO₂S)₂]. The structure of the complex was elucidated for the first time by a single-crystal X-ray diffraction technique. Each deoxyalliin molecule coordinates in a bidentate N,S-mode to palladium(II) in a trans-configuration analogous to the platinum(II) deoxyalliin complex early reported. As the main result, the Pd-sac complex showed a selective anti-proliferative activity against melanoma (UACC-62, TGI = 63.5 µM), while both deoxyalliin and K₂PdCl₄ were inactive against all cell lines. Moreover, Pd-sac did not affect the proliferation of non-tumorigenic keratinocytes (HaCaT, TGI > 586 µM) and was non-mutagenic in the Ames assay. The results open new perspectives for in vivo studies concerning the application of the Pd-sac complex in the treatment of melanoma.

Selenium (Se) is an essential trace element; however, excessive exposure may cause adverse effects because of its narrow safety margin. This study evaluated the toxicological and genotoxic effects of Se-biofortified broccoli seedlings in male and female Swiss mice. Animals received control or Se-enriched broccoli seedlings orally for 40 days (15, 45, or 70 µg Se/kg body weight (BW)). General toxicity (body weight gain), hematological (complete blood count), biochemical (creatinine, bilirubin, aspartate aminotransferase, alanine aminotransferase, and urea), histopathological, and micronucleus evaluations were performed. No significant changes in body weight or hematological parameters were detected. Biochemical alterations were restricted to males, with increased urea (51.90 ± 2.14 mg/dL) and decreased aspartate aminotransferase (128.4 ± 14.45 U/L) after 45 µg Se/kg BW. The highest Se dose increased spleen (0.60 ± 0.04 g/100 g BW) and ovary (0.29 ± 0.03 g/100 g BW) weights in females, decreased liver weight (5.82 ± 0.10 g/100 g BW), increased testis weight (0.76 ± 0.04 g/100 g BW) in males, induced renal and splenic histological alterations, and increased micronucleated polychromatic erythrocytes (0.46 ± 0.04). These findings indicate that 15 µg Se/kg BW was the safest dose evaluated. Future studies should investigate Se speciation and sex-dependent toxicological responses.