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

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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.

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Acknowledgments

The authors gratefully acknowledge Ms. C. D. Mohanapriya, Application Specialist, Central Research Facility, Sri Ramachandra Medical College and Research Institute, Chennai-600 116, Tamil Nadu, India for her valuable help in RT-PCR analysis.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India

    Veerasamy Vinothkumar, Shanmugam Manoharan & Ganapathy Sindhu

  2. Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Rajah Muthiah Dental College and Hospital, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India

    Madhavan Ramados Nirmal

  3. Department of Human Genetics, Sri Ramachandra Medical College and Research Institute, Chennai, 600 116, Tamil Nadu, India

    Venkatesan Vetrichelvi

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  1. Veerasamy Vinothkumar
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Correspondence to Shanmugam Manoharan.

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Vinothkumar, V., Manoharan, S., Sindhu, G. et al. Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 369, 17–25 (2012). https://doi.org/10.1007/s11010-012-1364-1

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