Efficacy of Caffeic Acid Phenethyl Ester (CAPE) in skin B16-F0 melanoma tumor bearing C57BL/6 mice

In current work, we investigated the in-vitro efficacy of Caffeic acid Phenethyl Ester (CAPE) as an anti-melanoma agent in five melanoma cell lines B16-F0, B16F10, SK-MEL-28, SK-MEL-5, and MeWo and in-vivo efficacy study in skin B16-F0 melanoma tumor model in C57BL/6 mice. The IC50 (48 h) of CAPE in above five melanoma cell lines was 15 A mu M. CAPE (20-200 A mu M) led to intracellular GSH depletion of 16-54%, and 10-25 fold increase in Reactive Oxygen Species (ROS) formation in B16-F0 cells. CAPE (15-30 A mu M) caused 5-7 fold increase in apoptosis in B16-F0 cells. CAPE (10, 20 and 30 mg/Kg/day) led to tumor size growth inhibition by 39 A +/- 33%, 54 A +/- 36%, and 57 A +/- 18%, respectively. The respective therapies led to plasma Alanine Amino Transferase (ALT) levels corresponding to 85 A +/- 18, 107 A +/- 26, 154 A +/- 35 IU/L in comparison to controls 66 A +/- 14 IU/L. At corresponding doses, the lipid peroxidation levels as measured by malondialdehyde (MDA) formation in liver homogenates were 255 A +/- 8 mu M, 304 A +/- 21 mu M, and 342 A +/- 14 mu M in comparison to 208 A +/- 6 mu M in controls. The level of MDA in kidney homogenates was 263 A +/- 21 mu M, 282 A +/- 18 mu M, and 350 A +/- 28 mu M, respectively, in comparison to 212 A +/- 8 mu M in controls. Administration of CAPE (10, 20, 30 mg/Kg/day) diminished free thiol contents in liver for 21 A +/- 15%, 40 A +/- 17%, and 44 A +/- 19% and in kidney homogenates for 25 A +/- 15%, 37 A +/- 18%, and 40 A +/- 22%, respectively, as compared to controls. Our study suggests that CAPE at 10 mg/Kg/day has significant anti-melanoma efficacy with minimal toxicity.