The primary research objective of this laboratory is to understand the molecular events involved in chemoprevention of skin cancer using the bioflavonoid, apigenin. Apigenin is present in fruits and vegetables and has been shown to be an inhibitor of mouse skin carcinogenesis induced by UVB- irradiation or the two-stage regimen of DMBA/TPA initiation/promotion. We are currently examining signal transduction and transcriptional pathways responsible for this antitumor activity.
p53 is a tumor suppressor protein that induces cell cycle arrest or apoptosis in cells containing DNA damage. We are investigating the signal transduction pathways and functional consequences of apigenin-mediated activation of p53. These pathways are being characterized using a variety of molecular techniques including site-directed mutagenesis, western analysis and RNAi technology. Our efforts are also focused on exploring the signal transduction and transcriptional pathways involved in UV- and TPA- induced cyclooxygenase-2 (COX-2) expression. COX-2 is frequently overexpressed in many types of cancer and inhibition of COX-2 significantly blocks tumor development. We believe that part of the chemopreventive action of apigenin may be explained by its ability to block activation of Akt kinase and synthesis of COX-2. Our goal is to develop apigenin and/or apigenin-derivatives as novel agents for chemoprevention of skin cancer.
Tong, X., Van Dross, R.T., Abu-Yousif, A., Morrison, A.R. and J.C. Pelling (2007). Apigenin Prevents UVB-Induced Cyclooxygenase-2 Expression: Coupled mRNA Stabilization and Translational Inhibition. Molecular and Cellular Biology 27(1):283-96.
Van Dross, R.T., Hong, X., Essengue, S., Fischer, S.M. and Jill C. Pelling (2006). Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by apigenin in mouse keratinocytes: Role of USF transcription factors. Molecular Carcinogenesis 46(4):303-14.
Van Dross, R., Browning, P.J. and J.C. Pelling (2006). Do Truncated Cyclins Contribute to Aberrant Cyclin Expression in Cancer? Cell Cycle 5(5):472-477.
Van Dross, R.T., Hong, X. and Jill C. Pelling (2005). Inhibition of TPA- Induced Cyclooxygenase-2 (COX-2) Expression by Apigenin through Down- Regulation of Akt Signal Transduction in Human Keratinocytes. Molecular Carcinogenesis 44(2): 83-91.
Van Dross, R.T.,
, S. Asad
, G., Mays, D.J., Barquero
, L., Duell
, S., Pietenpol
, J.A. and P.J. Browning (2005). Constitutively Active K-cyclin/cdk6 Kinase
in Kaposi’s Sarcoma-Associated Herpesvirus
-Infected Cells. Journal of the National Cancer Institute 97(9): 656-66.
Van Dross, R., Xue, Y., Knudson, A. and Jill C. Pelling (2003). The Chemopreventive Bioflavonoid Apigenin Modulates Signal Transduction Pathways in Keratinocyte and
carcinoma Cell Lines. The Journal of Nutrition 133: 3800S-3804S.
Van Dross, R.T. and M. Sanders (2002). Molecular Characterization of Recombinant Pneumocystis carinii DNA Topoisomerase I: Differential Interactions with Human Topo I Poisons and Pentamidine. Antimicrobial Agents and Chemotherapy 46(7): 2145-2154.
Van Dross, R.T., Rao K., Eisenberg, E. and Sanders, M. (1997). Cloning and Characterization of the Aspergillus nidulans DNA Topoisomerase I gene. Gene 203: 169-174.