Effects of Curcumin Derivatives on Tube-formation of Rat Lymphatic Endothelial Cells and Intracellular Signal Transduction

Curcumin and some of its derivatives were known to exhibit a variety of pharmacologic effects including anti-inflammatory, anti-cancer and anti-metastatic properties [1,2,3]. In the present study, two novel curcumin derivatives, L01 and L02 , were synthesized and examined for anti-angiogenic effect and influence on signal transduction pathways. L01 , L02, and curcumin inhibited the tube formation of the rat lymphatic endothelial TR-LE cells in a dose-dependent manner without affecting cell viability. L01 showed the most potent inhibitory effect with an IC 50 of 0.9µM followed by L02 and curcumin with IC 50 of 1.35 and 2.9µM, respectively. To investigate the molecular mechanisms involved, Western blot analysis revealed that all of the test compounds inhibited the phosphorylation of Akt, but not JNK and Erk, in TR-LE cell. L01 , the most potent compound, completely inhibited phosphorylation of AKT at 3µM while curcumin and L02 inhibited phosphorylation of AKT at the higher concentration of 10µM. The intracellular signal transduction supported that L01 and L02 exert anti-lymphangiogenesis action partly through Akt pathway. These results indicate that L01 and L02 are the potential lead compounds for the further development of anti-angiogenic drugs. Acknowledgements: Japanese-Thai Collaboratetive Scientific Research Fellowship (JSPS-NRCT) 2006 References: [1] Maheshwari, R.K. et al. (2006) Life Sci 78: 2081–2087. [2] Sharma, R.A., Gescher, A.J., Steward, W.P. (2005) Eur J Cancer 41: 1955–1968. [3] Ohashi, Y. et al. (2003) Oncology 65: 250–258.