Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.
Oral carcinogenesis, a multistep process with multifaceted etiology, arises due to accumulation of heterogeneous genetic changes in the genes involved in the basic cellular functions including cell division, differentiation, and cell death. These genetic changes in the affected cell progressively increase the cell proliferation, angiogenesis, and inhibition of apoptosis. The present study investigated the modulating effect of geraniol on the expression pattern of cell proliferative (PCNA, cyclin D1, c-fos), inflammatory (NF-κB, COX-2), apoptotic (p53, Bax, Bcl-2, caspase-3 and -9), and angiogenic (VEGF) markers in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5 % DMBA in liquid paraffin, three times a week, for 14 weeks, developed well-differentiated squamous cell carcinoma (SCC) in the buccal pouch of golden Syrian hamsters. All the hamsters treated with DMBA alone (100 %) developed oral tumors in the buccal pouch after 14 weeks. Over-expression of mutant p53, PCNA, Bcl-2, and VEGF accompanied by decreased expression of Bax were noticed in hamsters treated with DMBA alone. Increased expression of c-fos, COX-2, NF-κB, and cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration of geraniol at a dose of 250 mg/kg bw (body weight) not only completely prevented the formation of oral tumors but also prevented the deregulation in the expression of above mentioned molecular markers in hamsters treated with DMBA. The present results thus suggest that geraniol has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative, and apoptosis-inducing properties in DMBA-induced hamster buccal pouch carcinogenesis.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.
Veerasamy
V
Vinothkumar
Shanmugam
S
Manoharan
Ganapathy
G
Sindhu
Madhavan Ramados
MR
Nirmal
Venkatesan
V
Vetrichelvi
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000080462:Acyclic Monoterpenes; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D014408:Biomarkers, Tumor; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D013729:Terpenes / Q000008:administration & dosage*
D000080462:Acyclic Monoterpenes; D014408:Biomarkers, Tumor; D002273:Carcinogens; D013729:Terpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; C007836:geraniol