Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

Abstract

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.

d-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB

“…Ludwig et al [35] reported that mutant p53 gene and p53 protein expression has been reported in 30 to 50 % of mammary carcinogenesis. Detection of p53 protein by immunohistochemistry has become a routine method in pathology practice, and the presence of detectable p53 protein is an important prognostic marker that correlates with higher histopathologic grade, increased mitotic activity and aggressive behavior [63].…”

Curcumin‐free turmeric exhibits anti‐inflammatory and anticancer activities: Identification of novel components of turmeric

“…In addition to compounds discussed, monoterpenes from turmeric may also account for its activities. The most common of these monoterpenes are ascaridol , borneol , carvacrol , carvone , cymene , geraniol , limonene , linalool , α‐pinene , terpinolene , and thymol . Among these monoterpenes, carvacrol, geraniol, and limonene have received considerable attention over the years.…”

Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK

“…The present study showed that treatment with geraniol significantly weakened the caspase-3 and caspase-9 activities in SCI rats. Similarly, Vinothkumar et al (32) reported that geraniol modulated the apoptosis and inflammation by decreasing the activities of caspase-3 and caspase-9. Thus, the findings of the present study suggested that the anti-apoptotic effect of geraniol has an essential protective role in SCI.…”