ABSTRACT
OBJECTIVE: Mesenchymal stem cells (MSCs) derived exosomes offers several advantages as a cell-free therapeutic agents. In this study, Umbilical cord mesenchymal stem cells exosomes (UC-MSCs-exos) effects on oral squamous cell carcinoma (OSCC) cell line was evaluated. METHODS: UC-MSCs-exos were isolated and co-cultured with OSCC cells and their impact on OSCC was explored by various tests. Comet assay and western blot for cleaved caspase-3 and immunocytochemistry for caspase-8 were used for apoptosis assessment. HO-1 and Nrf2 were used to determine antioxidant levels. Tumor necrosis factor-α and interleukin-6 were assessed as inflammatory biomarkers. HOX transcript antisense intergenic long noncoding RNA (HOTAIR) expression was also evaluated. RESULTS: In a dose-dependent manner, UC-MSCs-exos reduced the levels of pro-inflammatory cytokines (IL-6 and TNF-α) and induced apoptosis of OSCC in vitro. Meanwhile, we found that UC-MSCs-exos downregulate HOTAIR. CONCLUSION: UC-MSCs-exos conferred a suppressive role on OSCC in vitro, highlighting a promising therapeutic role. However, the exact potentially involved molecules and molecular mechanisms need to be investigated in further studies.
Subject(s)
Carcinoma, Squamous Cell , Exosomes , Head and Neck Neoplasms , Mesenchymal Stem Cells , Mouth Neoplasms , Humans , Exosomes/metabolism , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Mouth Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Mesenchymal Stem Cells/metabolism , Umbilical Cord/pathologyABSTRACT
BACKGROUND: FOXD1 expression in oral squamous cell carcinoma remains uncovered. The aim was to detect the anticancer effect of Rosemary Extract RE through the evaluation of FOXD1 gene expression in (OSCC) by quantitative PCR. METHODS: OSCC cell line was served as a control group. Moreover, the OSCC cell line (SCC-15) was treated with RE (OSCC/ RE group) at 24, 48, and 72 hs time intervals. We assessed the antioxidant activity of RE by evaluation of lipid peroxidation (MDA) and superoxide dismutase (SOD) levels. The cytotoxic effects of RE were examined by MTT assay. mTOR and LC3 I/II autophagy protein markers were assessed by western blot. Apoptosis activity was assessed. RESULTS: The study results were statistically assessed. Intergroup comparisons were analyzed, whereas intragroup comparisons were conducted utilizing one-way repeated measures ANOVA, followed by multiple pairwise paired t-tests with Bonferroni correction revealed a significant increase of FOXD1 gene expression in the control OSCC group in comparison to the OSCC/RE group (p-value <0.001). A significant decrease of mTOR/LC3I/II proteins expression in the OSCC/RE group compared to the control OSCC group (p-value <0.001). CONCLUSION: FOXD1 can be considred a diagnostic biomarker for OSCC. RE inhibits autophagy of oral human cancer cells via mTOR/LC3I/II-dependent pathways and decrease caspase -3 apoptotic level.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Rosmarinus , Antioxidants/pharmacology , Apoptosis , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Proliferation , Forkhead Transcription Factors , Humans , Mouth Neoplasms/metabolism , Plant Extracts/pharmacology , Rosmarinus/metabolism , Signal Transduction , Squamous Cell Carcinoma of Head and Neck , Superoxide Dismutase/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
Salivary gland neoplasms exhibit complex histopathology in a variety of tumor types and treatment options depend largely on the stage of the cancer. Induced pluripotent stem cells (iPS) have been investigated for treating induced salivary gland cancer and for restoring salivary gland function. We investigated iPS treatment for salivary gland cancer both in vitro and in vivo. For our study in vitro, we re-programmed human skin fibroblasts to form iPS cells using a plasmid containing Oct4, Sox2, L-MYC and LIN28. For our study in vivo, we used 30 white male albino rats divided into the following groups of 10: group 1 (control): rats were injected with phosphate-buffered saline (PBS), group 2 induced squamous cell carcinoma (SCC): rat submandibular glands were injected with squamous carcinoma cells (SCC), group 3 (induced SCC/iPS): SCC treated rats treated with 5 × 106 iPS cells. Submandibular glands from rats of all groups were examined histologically and real time PCR was performed for amylase, and COX I and COX II gene expression. We confirmed that submandibular gland specimens included tumor tissue before starting treatment with iPS. iPS treated cases exhibited regeneration of salivary glands, although minor degenerative and vascularization changes remained. The acinar cells regained their proper organization, but continued to exhibit abnormal activity including hyperchromatism. iPS cells may be useful for treating salivary gland carcinomas.
