A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer.

OBJECTIVE: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC). METHODS: Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. RESULTS: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. CONCLUSIONS: This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

A novel natural product, britanin, inhibits tumor growth of pancreatic cancer by suppressing nuclear factor-κB activation.

Pancreatic cancer has a high mortality rate and poor prognosis. The development of novel medicines for pancreatic cancer therapy is urgently need. Britanin is a bioactive sesquiterpene lactone, that exhibits excellent anti-inflammatory and antioxidant effects. However, the potential anti-tumour activity of britanin is also considerable. Hence, in this study, the in vitro and in vivo anti-pancreatic cancer effects of britanin were investigated. Several pancreatic cancer cell lines were applied to evaluate inhibition of proliferation, migration and NF-κB pathway in vitro. Then in vivo toxicity of britanin was evaluated in BALB/c mice. The in vivo inhibitory effects of britanin were investigated by bioluminescence imaging, traditional methods and histological analysis in a pancreatic cancer xenograft mouse model. The results showed that britanin exhibited effective anti-tumour actions both in vitro and in vivo. The IC50 values in PANC-1, BxPC-3 and MIA CaPa-2 cell lines were 1.348, 3.367 and 3.104 µmol/L, respectively, and cell proliferation and migration were significantly inhibited by britanin treatment. Western blotting demonstrated that NF-κB family proteins, such as P50, P65, and P-P65 were affected by britanin treatment. It is worth noting that the P-P65 protein, which regulates the expression of multiple factors downstream, was significantly decreased in britanin treated group. In vivo experiments verified that britanin could suppress the tumour progression in a pancreatic cancer xenograft mouse model, while the compound did not exhibit intolerable toxicity. In conclusion, britanin has remarkable potential treatment effects against pancreatic cancer, and it could be developed as a new agent for pancreatic cancer chemotherapy.

Britanin attenuates ovalbumin-induced airway inflammation in a murine asthma model.

We previously demonstrated the alleviation of ovalbumin (OVA)-induced airway inflammation by Inulae flos. In the present study, the effects of britanin, a sesquiterpene compound isolated from Inulae flos, were evaluated in an in vivo animal model for anti-asthma activity through observation of airway hyperresponsiveness (AHR), eosinophil recruitment, Th2 cytokine and IgE levels, and lung histopathology. Britanin administration effectively reduced AHR induced by aerosolized methacholine, airway eosinophilia, Th2 cytokines in bronchoalveolar lavage fluids and the supernatant of cultured splenocytes compared with OVA-induced mice. Histological studies showed that increased inflammatory cell infiltration and mucus secretion were reduced by britanin administration. Thus, britanin may have therapeutic potential for treating allergic asthma.

Suppressive effects of britanin, a sesquiterpene compound isolated from Inulae flos, on mast cell-mediated inflammatory responses.

Mast cells are central players in immediate-type hypersensitvity and inflammatory responses. In the present study, the effects of britanin on the passive cutaneous anaphylaxis (PCA) reaction in mice and on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced production of pro-inflammatory cytokines in human mast cell line (HMC-1) were evaluated. The oral administration of britanin (10-20 mg/kg) decreased the mast cell-mediated PCA reaction in IgE-sensitized mice. In the activity and mechanism of britanin in vitro assay, britanin suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner in HMC-1. In addition, britanin attenuated PMACI-induced activation of NF-κB as indicated by the inhibition of the degradation of IκBα, nuclear translocation of NF-κB, NF-κB/DNA binding activity assay, and blocked the phosphorylation of p38 MAP kinase, in a dose-dependent manner. We conclude that britanin may have potential as a treatment for allergic-inflammatory diseases.