Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis.

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I-V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1-induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research.

MicroRNA-145-5p modulates Krüppel-like factor 5 and inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma.

BACKGROUND: In several human cancers, Krüppel-like factor 5 (KLF5), a zinc finger transcription factor, can contribute to both tumor progression or suppression; however, the precise role of KLF5 in nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, the association between KLF5 and microRNA-145-5p (miR-145-5p) in NPC cells was elucidated. RESULTS: Our results showed that KLF5 expression was up-regulated in NPC group compared to normal group. We found that KLF5 exhibited an oncogenic role in NPC cells. The upregulation of miR-145-5p inhibited the proliferation, migration, and invasion of NPC cells. It was observed that miR-145-5p could down-regulate the mRNA and protein expression of KLF5 in NPC cell lines. Additionally, the activity of focal adhesion kinase (FAK), a migration marker, was regulated by miR-145-5p and KLF5 in NPC cells. CONCLUSIONS: The results of this study indicated that miR-145-5p could repress the proliferation, migration, and invasion of NPC cells via KLF5/FAK regulation, and could be a potential therapeutic target for patients with NPC.

The antimicrobial peptide tilapia piscidin 3 induces mitochondria-modulated intrinsic apoptosis of osteosarcoma cells.

Osteosarcoma (OS) is the most common solid tumor of the bone that most often affects adolescents. The introduction of chemotherapy for the treatment of OS has largely improved the survival rates of patients with localized tumors. However, the 5-year survival rate of OS patients with relapsed or metastatic disease is only 10 to 20%. In this study, the antimicrobial peptide tilapia piscidin 3 (TP3), isolated from Nile tilapia (Oreochromis niloticus), was treated to OS MG63 cells. Our findings showed that TP3 concentration as low as 1 µM induced significant inhibition of cell viability and increased DNA fragmentation, as determined by the MTT and TUNEL assays, respectively. The protein expression levels of cleaved caspases 3/9 were increased. An in situ live-cell time-lapse video and cell tomographic microscopy images showed cellular blebbing, shrinkage, nuclear fragmentation, and chromatin condensation, with the formation of beaded apoptopodia. Moreover, there were significant increase in the production of TP3-induced mitochondrial and cellular reactive oxygen species (ROS), as well as down-regulated mitochondrial oxygen consumption and extracellular acidification rates. Additionally, TP3 enhanced mitochondrial fission, whereas fusion was attenuated. Furthermore, after administration of the mitochondria targeted antioxidant mitoTempo, TP3-induced ROS oxidant levels and alterations in cleaved caspases 3/9 expression were rescued. TP3 promoted mitochondria-modulated intrinsic apoptosis through the induction of ROS production, activation of caspases 3/9, and the down-regulation of mitochondrial oxygen consumption and extracellular acidification rates, suggesting that TP3 has potential as an innovative alternative for OS treatment.

Fragilides U-W: New 11,20-Epoxybriaranes from the Sea Whip Gorgonian Coral Junceella fragilis.

Three new 11,20-epoxybriaranes-fragilides U-W (1-3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1-3 were elucidated by spectroscopic methods and briaranes 3 and 5 displayed inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW264.7.

Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling.

Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug-resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4',6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long-term oral cancer prevention in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845-855, 2017.

Acute fulminant invasive fungal sinusitis with cavernous sinus syndrome.

Acute fulminant invasive fungal sinusitis is most commonly found in immunocompromised patients with conditions such as diabetes mellitus, malignancies and acquired immune deficiency syndrome. The most common pathogens are Aspergillus and Mucoraceae and the sinus most frequently involved is the maxillary sinus. Fever, rhinorrhea, facial pain, headache, and diplopia are common presenting symptoms. Complications of this infection include intracranial and / or intraorbital spread of the infection; the prognosis is poor. Here, a rare case of acute fulminant invasive fungal sinusitis with cavernous sinus syndrome is reported.

Lobular capillary hemangioma of the nasal cavity: a retrospective study of 15 cases in taiwan.

BACKGROUND: Lobular capillary hemangioma of the nasal cavity is an uncommon benign vascular tumor of unknown etiology. There have been only very few case reports in Taiwan. AIMS: This study aimed to analyze the clinical features, radiological findings, treatment modalities, and outcome of lobular capillary hemangioma treated at a teaching hospital in Taiwan during a period of 10 years. STUDY DESIGN: Descriptive study. METHODS: Retrospective chart reviews were performed on patients who were diagnosed with lobular capillary hemangioma of the nasal cavity at Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, from January 2003 to December 2012. Data retrieved included age, gender, clinical symptoms, computed tomography (CT) findings, treatment modalities, and outcome for further analysis. RESULTS: Of the 15 patients identified, there were five males and ten females ranging from 17 to 86 years of age, with a mean age of 43.8±20.2. Epistaxis was the most common presenting symptom. All patients presented a unilateral nasal lobular capillary hemangioma. The most commonly affected site was the anterior nasal septum, followed by the inferior turbinate, vestibule, middle turbinate, and posterior nasal septum. All lesions presented as soft tissue density without bony erosions under CT examination. Endoscopic excisional surgery (n=12) or classical local excision (n=3) was performed for complete removal of the hemangioma. No evidence of recurrence was observed with 6 to 75 months of follow-up. CONCLUSION: Lobular capillary hemangioma of the nasal cavity was usually found to occur in anterior septum with epistaxis. Complete excision with endoscopic surgery or classical local excision was recommended and recurrence can be prevented.

Influences of patient age on deep neck infection: clinical etiology and treatment outcome.

OBJECTIVES: To analyze the differences in clinical features, etiology, treatment modalities, and microbiology of the deep neck infections between the elderly and the adults. STUDY DESIGN: Cases series. SETTING: Single hospital. SUBJECTS AND METHODS: A retrospective review was performed on patients older than 18 years of age with diagnosis of deep neck infection from January 2008 to December 2012. A total of 148 patients were enrolled in this study, including 32 elderly (older than 65 years of age) and 116 adults who aged between 18 and 65. Data collected included age, gender, clinical presentations, etiology, treatment modalities, and microbiology. RESULTS: Odontogenic and salivary origin were the most common sources of infection for the elderly group, whereas the odontogenic and tonsillar origin were the most common sources of deep neck infections in the adult group. Compared to the adult group, the elderly group had significantly higher ratio with multiple spaces involved (53.1% vs 30.2%, P = .016), complication (15.6% vs 4.3%, P = .024), and surgical interventions (75.0% vs 38.8%, P < .001), in addition to longer hospital stay (11.1 ± 7.2 days vs 8.2 ± 4.5 days, P = .029). CONCLUSION: Compared to the adult group, the elderly patients with deep neck infection had more cases with multiple spaces involvement, complications, surgical interventions, and longer hospital stay. However, the outcome of the elderly group was the same as the adult group. Therefore, the benefits of aggressive management for deep neck infection should not be withheld from patients simply because of the old age.