Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3ß-dependent Snail degradation.

PURPOSE: PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. METHODS: The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. RESULTS: Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3ß-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3ß/Snail/vimentin axis. CONCLUSION: The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

PD-L1 Expression Correlated with Clinicopathological Factors and Akt/Stat3 Pathway in Oral SCC.

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that inhibits immune responses. The physiological and prognostic role of the PD-L1 signaling pathway in the oral maxillofacial region is unclear. This study aimed to investigate the role of PD-L1 in the progression of oral squamous cell carcinoma (OSCC). Furthermore, clinicopathological factors related to PD-L1 expression were examined in patients with OSCC through immunohistochemistry (IHC) of tissue sections and through an in vitro study in OSCC cells. The medical records, radiographic findings, and mortality referrals of 81 patients obtained from the National Statistical Office were reviewed. IHC was performed on tissue specimens of these patients to determine the expression levels of PD-L1, which showed significant statistical differences based on age, tumor size, TNM stage, cervical lymph node metastasis, and locoregional recurrence. Patients with a high PD-L1 expression had significantly poorer survival rates. Multivariate analysis using the Cox proportional model confirmed the high relative risk ratio for high PD-L1 expression, TNM stage, and neck node metastasis, all of which were significantly associated with a poor prognosis in patients with OSCC. The in vitro study showed that SAS and YD38 cells transfected with PD-L1 siRNA had significantly increased apoptosis, reduced proliferative capacity, and tumorigenicity.

Withaferin A mitigates metastatic traits in human oral squamous cell carcinoma caused by aberrant claudin-1 expression.

Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.

Non-thermal plasma application enhances the recovery of transected sciatic nerves in rats.

This experimental research aimed to investigate the effects of non-thermal plasma on nerve regeneration after transected nerve damage using the sciatic nerve in Wistar albino (A) rats. The experiments were performed on 27 Wistar A rats. The rats underwent surgery for right sciatic nerve exposure and were divided into three groups (each group, n = 9) according to sciatic nerve transected injury (SNTI) and non-thermal plasma application: a non-nerve damage (non-ND) group, a only nerve damage without non-thermal plasma application (ND) group, and a nerve damage with non-thermal plasma application (ND + NTP) group. Subsequent to SNTI and immediate suture, non-thermal plasma was administered three times per week for eight weeks. Evaluation for functional recovery was performed using the static sciatic index measured over the full treatment period of eight weeks. The sciatic nerve specimens were obtained after euthanasia and third day from the last non-thermal plasma application. The sciatic nerve tissues were subjected to histological analysis. Behavior analysis presented that the ND + NTP group showed improved static sciatic index compared with the nerve damage group. Histopathological findings demonstrated that the ND + NTP group had more dense Schwann cells and well-established continuity of nerve fibers, greater than the nerve damage group. Immunohistochemistry showed that the ND + NTP group had increased levels of markers for microtubule-associated protein 2 (MAP2), tau, S100 calcium-binding protein B, and neurofilament-200 and regulated the overexpression of CD68 and MAP2. These results indicated that non-thermal plasma enhanced the motor function and restored the neuronal structure by accelerating myelination and axonal regeneration. Additionally, non-thermal plasma was confirmed to have a positive effect on the recovery of SNTI in rats.

Targeting X chromosome-linked inhibitor of apoptosis protein in mucoepidermoid carcinoma of the head and neck: A novel therapeutic strategy using nitidine chloride.

Nitidine chloride (NC) was recently reported to exhibit a wide range of pharmacological properties for several diseases, including cancer. Here we report for the first time that NC is a potential therapeutic agent for mucoepidermoid carcinoma (MEC) occurring in the head and neck because it suppresses X chromosome-linked inhibitor of apoptosis protein (XIAP) in human MEC in vitro and in vivo. The antitumor effects of NC were evaluated by trypan blue exclusion assay, western blotting, live/dead assay, 4',6-diamidino-2-phenylindole (DAPI) staining, human apoptosis antibody array, immunofluorescence staining, immunohistochemistry, small interfering RNA assay, transient transfection of XIAP overexpression vector, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and histopathological examination of organs. NC inhibited cell viability and induced caspase-dependent apoptosis in vitro. A human apoptosis antibody array assay showed that XIAP is suppressed by NC treatment. XIAP was overexpressed in oral squamous cell carcinoma (OSCC) tissues that arose from the head and neck, and high XIAP expression was correlated with poor prognosis in OSCC patients. XIAP depletion significantly increased apoptosis, and ectopic XIAP overexpression attenuated the apoptosis induced by NC treatment. NC suppressed tumor growth in vivo at a dosage of 5 mg/kg/day. The number of TUNEL-positive cells increased and the protein expression of XIAP was consistently downregulated in NC-treated tumor tissues. In addition, NC caused no histopathological changes in the liver or kidney. These findings provide new insights into the mechanism of action underlying the anticancer effects of NC and demonstrate that NC is a promising therapeutic agent for the treatment of human MEC of the head and neck. KEY MESSAGES: • Nitidine chloride induces caspase-dependent apoptosis in MEC of the head and neck. • High XIAP expression correlates with poor prognosis of OSCC patients. • Nitidine chloride suppresses tumor growth in vivo without any systemic toxicities. • Targeting XIAP is a novel chemotherapeutic strategy for MEC of the head and neck.

Visfatin Induces Senescence of Human Dental Pulp Cells.

Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin, is closely associated with cellular senescence. However, little is known about the effect of visfatin on the senescence of human dental pulp cells (hDPCs). Here, it was found that in vivo visfatin levels in human dental pulp tissues increase with age and are upregulated in vitro in hDPCs during premature senescence activated by H2O2, suggesting a correlation between visfatin and senescence. In addition, visfatin knockdown by small interfering RNA led to the reduction in hDPC senescence; however, treatment with exogenous visfatin protein induced the senescence of hDPCs along with increased NADPH consumption, which was reversed by FK866, a chemical inhibitor of visfatin. Furthermore, visfatin-induced senescence was associated with both the induction of telomere damage and the upregulation of senescence-associated secretory phenotype (SASP) factors as well as NF-κB activation, which were all inhibited by FK866. Taken together, these results demonstrate, for the first time, that visfatin plays a pivotal role in hDPC senescence in association with telomere dysfunction and the induction of SASP factors.

Anti-inflammatory Effects of Sanguisorbae Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice.

OBJECTIVE: To investigate the anti-inflflammatory effects of Sanguisorbae Radix on contact dermatitis (CD). METHODS: Mice were sensitized by painting 30 µL of 1-fluoro-2,4-dinitrofluorobenzene (DNFB) onto each ear for 3 days. Four days later, mice were challenged by painting with 50 µL of DNFB onto the shaved dorsum every 2 days. Sanguisorbae Radix methanol extract (MESR) was applied onto the shaved dorsum every 2 days. The effects of MESR on skin thickness, skin weights, histopathological changes, skin lesions and cytokine production in DNFB-induced CD mice were investigated, as well as its effects on body weights and spleen/body weight ratio. RESULTS: Topical application of MESR effectively inhibited enlargement of skin thickness and weight (P<0.05). MESR treatment also inhibited hyperplasia, spongiosis and immune cell infiltration induced by DNFB in inflamed tissues and improved lesions on dorsum skin in CD mice. Moreover, treatment with MESR suppressed the increase in the levels of tumor necrosis factor α (TNF-α,P<0.01) and interferon γ (IFN-γ,P<0.05), respectively. Finally, MESR had no effect on body weight gain or spleen/body weight ratio. CONCLUSION: These data suggest that MESR acts as an anti-inflflammatory agent that decreases the production of TNF-α and IFN-γ, resulting in reductions of skin lesions and histopathological changes in inflamed skin tissues.

Whitlockite Granules on Bone Regeneration in Defect of Rat Calvaria.

Whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12) is a calcium phosphate based ceramic that contains magnesium ions. As the second most abundant mineral in living bone, WH occupies 25-35 wt % of the inorganic portion of human bone. Compared to hydroxyapatite (HAp, Ca10(PO4)6(OH)2), WH possesses better mechanical properties, faster resorbability, and promotion behavior on the osteogenesis. In this article, we introduced a fabrication method of interconnected porous WH granules through vacuum filtration, followed by sintering treatment based on the thermal stability of WH synthesized using the tri-solvent system. This study presents a histological, radiological, and immunohistochemical evaluation of the bone healing potential of these WH granules in a 5 mm diameter calvarial bone defect in rats. The histological evaluation shows no inflammation or foreign body reaction in the WH group. The WH group displays newly formed bone at the same thickness as the original bone. On the contrary, bone formation is not observed in the nontreated (NT) group. Besides, immunohistochemistry (IHC) confirmed that WH granules promoted bone regeneration with the significantly higher expression of bone morphogenetic proteins-2 (BMP-2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) compared to the NT group without the addition of exogenous cells or growth factors. These results suggest that WH has excellent potential for application in bone tissue regeneration.

Langerhans cell histiocytosis of the mandible: two case reports and literature review.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of dendritic cells resulting in local or systemic symptoms. The clinical symptoms of patients with Langerhans cell histiocytosis depend on the site and the degree of involvement. This article describes two case histories of unifocal bony Langerhans cell histiocytosis with mandibular involvement and further discusses the appropriate management of such via a review of the literature.

Misdiagnosis of ameloblastoma in a patient with clear cell odontogenic carcinoma: a case report.

Clear cell odontogenic carcinoma (CCOC), a rare tumor in the head and neck region, displays comparable properties with other tumors clinically and pathologically. In consequence, an incorrect diagnosis may be established. A 51-year-old male patient who was admitted to the Department of Oral and Maxillofacial Surgery at Pusan National University Dental Hospital was initially diagnosed with ameloblastoma via incisional biopsy. However, the excised mass of the patient was observed to manifest histopathological characteristics of ameloblastic carcinoma. The lesion was ultimately diagnosed as clear cell odontogenic carcinoma by the Department of Oral Pathology of Pusan National Dental University. Therefore, segmental mandibulectomy and bilateral neck dissection were performed, followed by reconstruction with fibula free flap and reconstruction plate. Concomitant chemotherapy radiotherapy was not necessary. The patient has been followed up, and no recurrence has occurred 6 months after surgery.

Retrospective clinical study of multiple keratocystic odontogenic tumors in non-syndromic patients.

OBJECTIVES: A keratocystic odontogenic tumor (KOT) is a type of odontogenic tumor that mainly occurs in the posterior mandible. Most KOTs appear as solitary lesions; however, they sometimes occur as multiple cysts. This study analyzed the clinical features of multiple KOTs. MATERIALS AND METHODS: The participants were diagnosed with KOT by biopsy with multiple surgical sites, and were patients at the Pusan National University Hospital and the Pusan National University Dental Hospital from January 1, 2005 to March 31, 2016. Charts, records, images and other findings were reviewed. RESULTS: A total of 31 operations were conducted in 17 patients. The mean patient age was 28.4±20.1 years. Multiple KOTs were found to occur at a young age (P<0.01). The predominant sites were in the posterior mandible (28.6%). Most cases of multiple lesions appeared in both the upper and lower jaw, and 40.3% of lesions were associated with unerupted and impacted teeth. The overall recurrence rate measured by operation site was 10.4% (8/77 sites). No patients were associated with nevoid basal cell carcinoma syndrome. CONCLUSION: The pure recurrence rate was lower than estimated, but there was a higher possibility of secondary lesions regardless of the previous operation site; therefore, long-term follow-up is necessary.

Ataxia-Telangiectasia-Mutated Protein Expression as a Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands.

PURPOSE: Adenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC. MATERIALS AND METHODS: In this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis. RESULTS: Myb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017). CONCLUSION: These data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands.

The Flavonoid Jaceosidin from Artemisia princeps Induces Apoptotic Cell Death and Inhibits the Akt Pathway in Oral Cancer Cells.

Jaceosidin is a single compound from the Japanese mugwort Artemisia princeps, which is used as a food and a traditional medicinal herb. A. princeps extracts and flavonoid components have been shown to have antihyperglycaemic, antioxidant, and anti-inflammatory properties. Although the anticancer properties of these extracts were recently demonstrated, the related mechanisms have not been characterised. In this study, we investigated the effects of jaceosidin in oral squamous cell carcinoma (OSCC) cells and initially showed selective suppression of proliferation (IC50 = 82.1 µM in HSC-3 cells and 97.5 µM in Ca9.22 cells) and accumulation of cells at the sub-G1 stage of the cell cycle. In addition, jaceosidin increased cleavage of caspase-9 and caspase-3 in OSCC cells, although caspase-8 was not detected. In further experiments, jaceosidin downregulated Akt phosphorylation and ectopic activation of Akt blocked the antiproliferative effects of jaceosidin. Finally, we showed that jaceosidin has no effects on HaCaT normal epithelial cell viability, indicating selective chemotherapeutic potential of jaceosidin and that tumour-specific downregulation of Akt increases apoptosis and inhibits growth in OSCC cells.

Reconstruction of cheek mucosal defect with a buccal fat pad flap in a squamous cell carcinoma patient: a case report and literature review.

BACKGROUND: Squamous cell carcinoma (SCC) is the most commonly occurring malignant tumor in the oral cavity. In South Korea, it occurs most frequently in the mandible, tongue, maxilla, buccal mucosa, other areas of the oral cavity, and lips. Radial forearm free flap (RFFF) is the most widely used reconstruction method for the buccal mucosal defect. The scar of the forearm donor, however, is highly visible and unsightly, and a secondary surgical site is needed when such technique is applied. For these reasons, buccal fat pad (BFP) flap has been commonly used for closing post-surgical excision sites since the recent decades because of its reliability, ease of harvest, and low complication rate. CASE PRESENTATION: In the case reported herein, BFP flap was used to reconstruct a cheek mucosal defect after excision. The defect was completely covered by the BFP flap, without any complications. CONCLUSION: Discussed herein is the usefulness of BFP flap for the repair of the cheek mucosal defect. Also, further studies are needed to determine the possibility of using BFP flap when the defect is deep, and the maximum volume that can be harvested considering the changes in volume with age.

Chinese medicines reported to have effects on contact dermatitis in the last 20 years.

Contact dermatitis (CD) is one of the most common skin diseases in industrialized countries. Chinese medicines (CMs) have been investigated worldwide as complementary and alternative medicines for corticosteroids, which are the first choice for treatment of inflflammatory skin diseases owing to their favorable efficacy. This article describes the CMs that have been reported to have anti-dermatitis effects against CD in the last 20 years.

Nitidine chloride acts as an apoptosis inducer in human oral cancer cells and a nude mouse xenograft model via inhibition of STAT3.

Nitidine chloride (NC) is a natural alkaloid compound derived from the plant Zanthoxylum nitidum and is known for its therapeutic anticancer potential. In this study, we investigated the effects of NC on growth and signaling pathways in human oral cancer cell lines and a tumor xenograft model. The apoptotic effects and related molecular targets of NC on human oral cancer were investigated using trypan blue exclusion assay, DAPI staining, Live/Dead assay, Western blotting, Immunohistochemistry/Immunofluorescence and a nude mouse tumor xenograft. NC decreased cell viability in both HSC3 and HSC4 cell lines; further analysis demonstrated that cell viability was reduced via apoptosis. STAT3 was hyper-phosphorylated in human oral squamous cell carcinoma (OSCC) compared with normal oral mucosa (NOM) and dephosphorylation of STAT3 by the potent STAT3 inhibitor, cryptotanshinone or NC decreased cell viability and induced apoptosis. NC also suppressed cell viability and induced apoptosis accompanied by dephosphorylating STAT3 in four other oral cancer cell lines. In a tumor xenograft model bearing HSC3 cell tumors, NC suppressed tumor growth and induced apoptosis by regulating STAT3 signaling without liver or kidney toxicity. Our findings suggest that NC is a promising chemotherapeutic candidate against human oral cancer.

Kochia scoparia induces apoptosis of oral cancer cells in vitro and in heterotopic tumors.

ETHNOPHARMACOLOGICAL RELEVANCE: Kochia scoparia grows commonly in China, Japan, and Korea and its mature fruit has been used throughout the area in traditional medicine to treat diseases including skin problems and inflammatory and allergic disease. More importantly, Kochia scoparia has been prescribed to treat the malignant tumor of head and neck region and breast mass. Although it has been proposed as an anti-cancer agent for several cancers, its exact in vivo anti-cancer properties and the molecular mechanisms underlying its effects are poorly understood. AIM OF THE STUDY: To evaluate the anti-cancer activity of the methanol extract of K. scoparia, mature fruit (MEKS) on oral squamous cell carcinoma (OSCC) and to explore its mode of action. MATERIALS AND METHODS: To assess proliferation inhibition and apoptosis induction by MEKS, MTT assays, cell analysis, ANNEXIN V and PI double staining, and Hoechst 33342 staining were performed. The activation of caspases and the MAP kinase p38 was evaluated using Western blot analysis. The anti-cancer properties of MEKS in vivo were elucidated in a heterotopic OSCC animal model. RESULTS: After OSCC cells were treated with MEKS, the numbers of sub-G1 accumulated cells and apoptotic bodies increased, indicating that MEKS inhibited OSCC cell proliferation selectively through induction of apoptosis. Apoptosis of MEKS-treated OSCC cells was induced in a dose-dependent manner by caspase-3 and -9 activation. In addition, pretreatment with p38 inhibitor SB203580 in combination with MEKS significantly prevented MEKS-induced apoptosis in OSCC cells and also decreased cleaved capase 3, 9, and cleaved PARP activity in western blotting. MEKS treatment significantly increased the apoptosis of OSCC and inhibited tumour growth in our animal model. CONCLUSION: Taken together, these results indicated that MEKS induced apoptosis of OSCC cells through caspase activation involving the p38 MAPK pathway. MEKS could be a promising anti-cancer candidate for OSCC treatment.

Anti-inflammatory activity of Kochia scoparia fruit on contact dermatitis in mice.

The mature fruit of Kochia scoparia (L.) Schrad. is widely administered in China and Korea as a medicinal herb for treatment of skin diseases, diabetes mellitus and rheumatoid arthritis. The present study investigated the effects of methanol extracts of K. scoparia dried fruit (MEKS) on ear swelling, histopathological changes (such as epidermal acanthosis, spongiosis and immune cell infiltration) and cytokine production in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mice. Topical application of MEKS inhibited DNFB-induced ear thickness and weight increases, as well as DNFB-induced epidermal acanthosis, spongiosis and immune cell infiltration. In addition, treatment with MEKS significantly decreased the levels of tumor necrosis factor-α, interferon-γ and monocyte chemotactic protein-1 in inflamed tissues. These data indicate that the mature fruit of K. scoparia has the potential to be administered for the treatment of inflammatory skin diseases and that the anti-inflammatory action of K. scoparia is involved in the inhibition of type 1 T helper cell skewing reactions.

Poncirus trifoliata Rafin. induces the apoptosis of triple-negative breast cancer cells via activation of the c-Jun NH(2)-terminal kinase and extracellular signal-regulated kinase pathways.

BACKGROUND: Poncirus trifoliata Rafin. is a traditional medicine with known anti-inflammatory and anti-cancer properties. Traditionally, it is used to control chronic inflammation, allergy and gastrointestinal diseases such as digestive ulcers gastritis in China, Japan, and Korea. OBJECTIVES: To evaluate the apoptosis-inducing activity of a P. trifoliata methanol extract (MEPT) and elucidate the molecular mechanisms. MATERIALS AND METHODS: The anti-cancer effect of MEPT and its underlying mechanisms were investigated in breast cancer cells using 3,4,5-dimethyl N-methylthiazol-2-yl-2, 5-d-phenyl tetrazolium bromide assay, cell cycle analysis, and western blotting. RESULTS: MEPT suppressed the proliferation of MDA-MB-231 cells with inhibition dose 50% value of 119.44 µg/mL at 24 h, which have features typical of triple-negative breast cancer cells. MEPT also altered the characteristic features of the MDA-MB-231 cells and increased the proportion of cells undergoing sub-G1 arrest. In addition, MEPT increased levels of caspase 8 and 3 in MDA-MB-231 cells, whereas caspase 9 was not detected. In addition, MEPT-induced tumor necrosis factor receptor (TNFR) and TNFR type 1-associated death domain (TRADD) protein and the activations of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK). CONCLUSION: Our results indicate that MEPT has chemotherapeutic potential in triple-negative breast cancer and that at the molecular level its effects are derived from the activations of TNFR and of the mitogen-activated protein kinase pathway.