ANTITUMOR AND CYTOTOXIC ACTIVITY OF GINGER ESSENTIAL OIL (ZINGIBER OFFICINALE ROSCOE)

Objective: To evaluate the cytotoxicty and antitumor activity of ginger essential oil (GEO).Methods: Cytotoxicity towards Dalton's Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) cell lines were evaluated by trypan blue exclusion method. In vitro cytotoxicity of GEO to L929 cells in culture were checked by MTT assay. The antitumor activity of GEO was determined by using DLA cell line induced solid tumor and EAC cell line induced ascites tumor model in mice and its comparison with standard anticancer drug cyclophosphamide.Results: GEO showed potent in vitro cytotoxic activity against DLA and EAC cell lines. IC50 value for DLA cell line was 11 μg/ml and for EAC cell lines 18 μg/ml. The IC50 of GEO was found to be 41 μg/ml against the L929 cell lines and to Vero cells was found to be ˃100 ug/ml. The treatment with GEO (500 mg/kg and 1000 mg/kg body weight) significantly reduced the volume of solid tumor development by 54.4% and 62.4% respectively. The life span was increased up to 50% in 1000 mg/kg b. wt GEO treated ascites tumor induced animals.Conclusion: This indicates the significant in vitro cytotoxic and antitumor properties of GEO suggesting its potential use as an anticancer agent.Â

Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies

Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol), as assessed by oral acute (5 g/kg b.wt. for 14 days) and subchronic (0.25, 0.5 and 1 g/kg b.wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of Clovinol did not result in any toxicologically significant changes in clinical/behavioural observations, ophthalmic examinations, body weights, organ weights, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals, indicating the no observed-adverse-effect level (NOAEL) as 1000 mg/kg b.wt./day; the highest dose tested. Terminal necropsy did not reveal any treatment-related histopathology changes. Clovinol did not show genotoxicity when tested on TA-98, TA-100 and TA-102 with or without metabolic activation; rather exhibited significant antimutagenic potential against the known mutagens, sodium azide, NPD and tobacco as well as against 2-acetamidoflourene, which needed metabolic activation for mutagenicity. Keywords: Syzygium aromaticum, Clove bud extract, Polyphenol, Subchronic toxicity, Mutagenicity, Genotoxicit

Beyond the flavor: A green formulation of Ferula asafoetida oleo-gum-resin with fenugreek dietary fibre and its gut health potential

Albeit the fact that asafotida is a popular kitchen spice and Indian folklore medicine for gut disorders, its consumption at physiologically relevant dosage is greatly challenged by the unpleasant flavor characteristics. Herein we report a green approach to derive stable powder formulations of asafoetida gum with minimized taste and odor suitable for dietary applications and gut health-related disorders. Employing a water based ultrasound mediated gel-phase dispersion of asafoetida gum on fenugreek derived soluble galactomannan fibre matrix. Microencapsulated particles (1 ± 0.3 μm) of asafoetida was prepared as water dispersible free flowing powder (Asafin). Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), accelerated stability and in vitro dissolution studies confirmed the stability, sustained release and microencapsulated structure of Asafin. Further investigations revealed significant (p < 0.01) reduction in acetic acid-induced writings and inhibition of ethanol-induced ulcer (94.1%) in rats orally administered with Asafin at 250 mg kgâ1 b.w. Asafin also exhibited anti-inflammatory effects (p < 0.01), in acute and chronic paw edema mice models. The safety of Asafin was further demonstrated by acute toxicity studies at 4 g kgâ1  b.w. and by 28 days of sub-acute toxicity studies at 2.0 g kgâ1 b.w. Keywords: Ferula asafoetida, Green formulation, Oral delivery, Gastroprotective, Ethanol-induced ulcer, Gut healt

Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer.

UNLABELLED: The survival rate for patients with head and neck cancer (HNC) diagnosed with cervical lymph node (cLN) or distant metastasis is low. Genomic alterations in the HRAS oncogene are associated with advanced tumor stage and metastasis in HNC. Elucidation of the molecular mechanisms by which mutated HRAS (HRASmut) facilitates HNC metastasis could lead to improved treatment options for patients. Here, we examined metastasis driven by mutant HRAS in vitro and in vivo using HRASmut human HNC cell lines, patient-derived xenografts, and a novel HRASmut syngeneic model. Genetic and pharmacological manipulations indicated that HRASmut was sufficient to drive invasion in vitro and metastasis in vivo. Targeted proteomic analysis showed that HRASmut promoted AXL expression via suppressing the Hippo pathway and stabilizing YAP1 activity. Pharmacological blockade of HRAS signaling with the farnesyltransferase inhibitor tipifarnib activated the Hippo pathway and reduced the nuclear export of YAP1, thus suppressing YAP1-mediated AXL expression and metastasis. AXL was required for HRASmut cells to migrate and invade in vitro and to form regional cLN and lung metastases in vivo. In addition, AXL-depleted HRASmut tumors displayed reduced lymphatic and vascular angiogenesis in the primary tumor. Tipifarnib treatment also regulated AXL expression and attenuated VEGFA and VEGFC expression, thus regulating tumor-induced vascular formation and metastasis. Our results indicate that YAP1 and AXL are crucial factors for HRASmut-induced metastasis and that tipifarnib treatment can limit the metastasis of HNC tumors with HRAS mutations by enhancing YAP1 cytoplasmic sequestration and downregulating AXL expression. SIGNIFICANCE: Mutant HRAS drives metastasis of head and neck cancer by switching off the Hippo pathway to activate the YAP1-AXL axis and to stimulate lymphovascular angiogenesis