Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Abstract

The present study has investigated the modulating effect of carnosic acid on the expression pattern of cell proliferative (proliferating cell nuclear antigen (PCNA) cyclin D1 and a transcription factor c-fos), apoptotic (p53, Bcl-2, Bax caspase -3 and 9), inflammatory (Nuclear factor kappa B (NFκB) and cyclooxygenase-2 (COX-2) and angiogenic (vascular endothelial growth factor (VEGF) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the hamsters buccal pouches by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Hundred per cent tumour formation (well-differentiated squamous cell carcinoma) accompanied by deregulation in the above mentioned molecular markers was noticed in hamsters treated with DMBA alone (tumour bearing hamsters). Oral administration of carnosic acid at dose of 10mg/kg bw to hamsters treated with DMBA not only completely prevented the tumour formation, but also corrected the abnormalities in the expression pattern of molecular markers. The present study suggests that carnosic acid might have inhibited the tumour formation by exerting anti-cell-proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.

Distinct Angiogenic Changes during Carcinogenesis Defined by Novel Label-Free Dark-Field Imaging in a Hamster Cheek Pouch Model

“…On the other hand, the increase in growth of small vessels in pre-cancer and cancer, which is characterized by rapid and chaotic sprouting of new, usually immature vessels, serves to provide nutrients to the proliferating cancer cells (25). Overexpression of VEGF has been observed in DMBA-treated hamster oral mucosa (26,27) as a marker of angiogenesis (28,29), suggesting that the changes we observed here are due in part to increasing VEGF over the course of neoplastic progression. Upregulation of other pro-angiogenic growth factors and endothelial receptor tyrosine kinases such as Tie2 likely contribute to these vascular abnormalities as well (30).…”

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

“…In DMBA-induced models of oral cancer using hamsters, it was shown that using 10 mg/kg/day CA administered orally for 14 weeks, caused the number of tumors on the animals to significantly decrease. Furthermore, expression of detoxification enzymes was enhanced [83], markers of apoptosis including p53, Bax, Bcl-2 and caspases were increased [84], and regulators of cell growth including COX-2, c-fos, KF-κB and cyclin D1 were decreased [84]. Using the same hamster model, 750 µg CA dissolved in 0.1mL saline (20 µM) administered daily for 11 weeks significantly slowed the progression of lesions and oral cancer development [85].…”

Thymol attenuates altered lipid metabolism in β-adrenergic agonist induced myocardial infarcted rats by inhibiting tachycardia, altered electrocardiogram, apoptosis and cardiac hypertrophy

“…In this, caffeic acid possesses antioxidant and anticarcinogenic properties (Senthil Kumaran, & Stanely Mainzen Prince, 2010), p-coumaric acid exhibits antioxidant, anti-inflammatory, free radical scavenging and anticancer properties (Roy & Prince, 2013b), ferulic acid contains antioxidant, free radical scavenging, anti-inflammatory, anticancer and neuroprotective properties (Barone, Calabrese, & Mancuso, 2009), carnosic acid possesses anti-inflammatory, antigenotoxic, antioxidant, and anti-carcinogenic properties (Rajasekaran et al, 2013), cinnamic acid exhibits antioxidant, free radical scavenging and anti-microbial properties (Sova, 2012) and naringenin possesses anti-diabetic, hepatoprotective, antioxidant and anti-inflammatory properties (Annadurai, Thomas, & Geraldine, 2013), which make thyme an excellent functional food for the prevention of various pathological features.…”