Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells.

Curcumin, a polyphenol isolated from the rhizome of Curcuma longa, has been studied because of its antioxidant, antimicrobial, and antiinflammatory properties. This study aimed to evaluate the effects of curcumin on head and neck cancer (HNC) cell lines and how it modulates the PI3K-AKT-mTOR signaling pathway. Dose-response curves for curcumin were established for hypopharynx carcinoma (FaDu), tongue carcinoma (SCC-9), and keratinocytes (HaCaT) cell lines and IC50 values were calculated. Cell cycle and cell death were investigated through flow cytometry. Cytoskeleton organization was assessed through phalloidin+FITC staining. qPCR array and western blot were performed to analyze gene and protein expression. Curcumin reduced cell viability in a dose-dependent and selective manner, induced cell death on SCC-9 cells (necrosis/late apoptosis: 44% curcumin vs. 16.4% vehicle), and arrested cell cycle at phase G2 /M on SCC-9 and FaDu (G2 : SCC-9-19.1% curcumin vs. 13.4% vehicle; FaDu-37.8% curcumin vs. 12.9% vehicle). Disorganized cytoskeleton and altered cell morphology were observed. Furthermore, curcumin downregulated the PI3K-AKT-mTOR signaling pathway by modifying the expression of key genes and proteins. These findings highlight the promising therapeutic potential of curcumin to inhibit HNC growth and progression and to modulate the PI3K-AKT-mTOR pathway.

The impact of photobiomodulation therapy on the biology and behavior of head and neck squamous cell carcinomas cell lines.

Photobiomodulation therapy (PBMT) is an emerging therapeutic modality designed to prevent and treat chemotherapy-driven oral mucositis (OM). However, the response of tumor cells to the effects of PBMT remains poorly understood. Our study explores the effects of PBMT in head and neck squamous cell carcinoma (HNSCC) based on cellular proliferation, migration, and survival of tumor cells and its population of cancer stem cells (CSC). We explored the behavior of two HNSCC cell lines (HN6 and HN13) under two distinct conditions, a physiological growing condition (10% FBS), and under stress growing condition (2% FBS) prior to irradiation using diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil). Diode laser (660 nm) was applied with a power of 100 mW delivering a total energy per point of 0.24 J. MTT and wound healing test (scratch assay) were performed to evaluate, respectively, proliferation and migration of tumor cells. Clonogenic and spheres formation assays were also performed to evaluate the survival and percentage of CSC upon irradiation. Overall, we observed that PBMT does not exacerbate the behavior of HNSCC. We could only observe a decrease in cellular proliferation of one cell line (HN6) when cultured under nutritional stress conditions (p < .05). There were no significant differences between the control and the PBMT groups regarding cell migration, survival and the percentage of CSC. Collectively, our results suggest that in vitro administration of PBMT to HNSCC does not modify the behavior of tumor cells.

Efficacy of laser phototherapy in comparison to topical clobetasol for the treatment of oral lichen planus: a randomized controlled trial.

Oral lichen planus (OLP) is a relatively common chronic mucocutaneous inflammatory disease and a search for novel therapeutic options has been performed. We sought to compare the efficacy of laser phototherapy (LPT) to topical clobetasol propionate 0.05% for the treatment of atrophic and erosive OLP. Forty-two patients with atrophic/erosive OLP were randomly allocated to two groups: clobetasol group (n=21): application of topical clobetasol propionate gel (0.05%) three times a day; LPT group (n=21): application of laser irradiation using InGaAlP diode laser three times a week. Evaluations were performed once a week during treatment (Days 7, 14, 21, and 30) and in four weeks (Day 60) and eight weeks (Day 90) after treatment. At the end of treatment (Day 30), significant reductions in all variables were found in both groups. The LPT group had a higher percentage of complete lesion resolution. At follow-up periods (Days 60 and 90), the LPT group maintained the clinical pattern seen at Day 30, with no recurrence of the lesions, whereas the clobetasol group exhibited worsening for all variables analyzed. These findings suggest that the LPT proved more effective than topical clobetasol 0.05% for the treatment of OLP.

Laser phototherapy triggers the production of reactive oxygen species in oral epithelial cells without inducing DNA damage.

Laser phototherapy (LPT) is widely used in clinical practice to accelerate healing. Although the use of LPT has advantages, the molecular mechanisms involved in the process of accelerated healing and the safety concerns associated with LPT are still poorly understood. We investigated the physiological effects of LPT irradiation on the production and accumulation of reactive oxygen species (ROS), genomic instability, and deoxyribose nucleic acid (DNA) damage in human epithelial cells. In contrast to a high energy density (20 J/cm²), laser administered at a low energy density (4 J/cm²) resulted in the accumulation of ROS. Interestingly, 4 J/cm² of LPT did not induce DNA damage, genomic instability, or nuclear influx of the BRCA1 DNA damage repair protein, a known genome protective molecule that actively participates in DNA repair. Our results suggest that administration of low energy densities of LPT induces the accumulation of safe levels of ROS, which may explain the accelerated healing results observed in patients. These findings indicate that epithelial cells have an endowed molecular circuitry that responds to LPT by physiologically inducing accumulation of ROS, which triggers accelerated healing. Importantly, our results suggest that low energy densities of LPT can serve as a safe therapy to accelerate epithelial healing.