ß-Caryophyllene promotes oxidative stress and apoptosis in KB cells through activation of mitochondrial-mediated pathway - An in-vitro and in-silico study.

Beta-caryophyllene (BCP), are natural bicyclic sesquiterpenes which are present in numerous plants worldwide. BCP has antioxidant, antimicrobial, and antifungal properties. Here, we studied its anticancer, anti-inflammatory, and cytotoxic effects. Cells treated with BCP, in a dose-dependent manner, exhibited morphological changes, showed lower cell growth, underwent apoptosis and lost the ability to metastasis through the suppression of NF-Ò¡ B via PI3K/AKT signalling pathway. These results elucidate that the inhibition of NF-Ò¡ B and PI3K/AKT is one of the most important mechanism by which BCP suppresses cancer cell proliferation and enhances apoptosis.

Modulating effect of hesperetin on the molecular expression pattern of apoptotic and cell proliferative markers in 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) is widespread malignant neoplasm and refractory cancers in worldwide. Here, we studied the chemopreventive potential of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs). Oral tumours were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA three times a week for 10 weeks. This causes sequentially hyperplasia, dysplasia and well differentiates squamous cell carcinoma (SCC) with up-regulation of molecular markers like mutant-p53, Caspase-3 and caspase-9 and cyclin-D1. Histology, immunohistochemistry (IHC), real time PCR (qRT-PCR) and western blot analysis of hesperetin treated animals shows a reversal in the above expression pattern to near normal in buccal mucosal tissue. Therefore, hesperetin exhibits the potential protective effect against DMBA-induced oral cancer through apoptotic and anti-proliferative properties. However, a long-term observation would be needed to confirm the possibility of malignant change of the resulted dysplastic lesions upon hesperetin pretreatment.

Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities in 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.

We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties.

Hesperetin on Cell Surface Glycoconjugates Abnormalities and Immunohistochemical Staining with Cytokeratin in 7,12 Dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis.

Hesperetin, a naturally occurring citrus flavanone of the bioactive substance, possesses different pharmacological and biochemical activities including anti-cancer and anti-oxidants effect. The aim of the study to investigate that hesperetin on abnormalities of glycoconjugates (protein bound hexose, hexosamine, total sialic acid and fucose), histology (PAS staining) and immunoexpression of cytokeratin during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) carcinogenesis. Oral tumors were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA thrice a week for 10 weeks and developed morphological alterations depicted as hyperplasia, dysplasia and well-differentiated squamous cell carcinoma formation with noticeable abnormalities of glycoconjugates and cytokeratin. The protective effect of hesperetin against DMBA was evaluated by assessing immunohistochemical expression, histological sections of buccal tissues and the levels of glycoconjugates in the buccal mucosa and plasma were analyzed. Hesperetin administrated orally at a dose of 20 mg/kg b.w. to hamsters treated with DMBA, significantly reduced the status of glycoconjugates and cytokeratin to the near normal range. Overall findings accomplished that hesperetin protects cell surface glycoconjugates abnormalities in DMBA induced HBP carcinogenesis.

Chemopreventive effect of syringic acid on 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.

Oral squamous cell carcinoma is most prevalent and refractory cancers worldwide. Recently, chemoprevention could be a promising approach in developing countries. The present study investigates the mechanism of syringic acid (SA), a phenolic constituent of plant Alpiniacalcarata Roscoe, and their leaves are used as traditional Indian Ayurveda medicines, mediated chemoprevention on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPC). Lipid peroxidation and antioxidants were measured in the plasma and buccal tissues in experimental hamsters. Modulating effect of SA on the expression pattern of PCNA, Cyclin D1, and mutant p53 markers was used for immunoexpression and western blotting analysis. In the present study, 100% tumor formation with marked abnormalities in the biochemical parameters of lipid peroxidation and antioxidants through up-regulation of molecular markers like PCNA, Cyclin D1, and mutant p53 was accompanied with tumor-bearing hamsters. Oral administration of SA at the doses of 50 and 100 mg/kg body weight (bw) to DMBA-treated hamsters significantly inhibited adverse changes in the biochemical parameters of the plasma and buccal mucosal tissues and also down-regulation of molecular marker expression (PCNA, Cyclin D1, and mutant p53). The present study thus suggests that SA has potent anti-lipid peroxidative, antioxidant, anti-cell proliferative, and apoptosis-inducing properties during DMBA-induced HBPC.

Molecular effects of hesperetin, a citrus flavanone on7,12-dimethylbenz(a)anthracene induced buccal pouch squamous cell carcinoma in golden Syrian hamsters.

In recent years, researchers have been focused on citrus flavanone, a naturally occurring bioactive substance of hesperetin. To investigate the molecular mechanism based chemopreventive efficacy of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) squamous cell carcinoma (SCC). The oral tumour was provoked by painted with 0.5% DMBA on left buccal pouch thrice a week for 10 consecutive weeks developed well-differentiated SCC and tumour formation was 100% in DMBA alone. We evaluated the chemopreventive potential of hesperetin by assessing the lipid peroxidation (LPO) by-products, status of enzymatic, non-enzymatic antioxidants, detoxifying agents etc. Moreover, modulating expression of apoptotic and cell proliferation markers were observed in HBP SCC experimental hamsters. Oral administration of hesperetin (20 mg/kg b.w.) to DMBA painted hamsters significantly reversed the stages of oral SCC. Our findings indicate that hesperetin possesses a chemopreventive effect in DMBA-induced oral SCC by exerting anti-carcinogenic property.