Responses of bromelain in a human cell screening assay for melanoma prevention

B145

A human cell chemoprevention assay has been developed in our laboratory to identify agents that alter biomarkers with relevance to melanoma development. The assay uses the radial growth phase-like melanoma cell line, WM3211, and co-exposure to 25 mJ/cm² UVB irradiation. E-cadherin induction and N-cadherin inhibition were included as biomarkers due to their relevance to the control normal melanocyte growth and differentiation and the changes in the N-cadherin/E-cadherin ratios during melanoma development. Given the importance of the E-cadherin/N-cadherin homeostatic tissue controls that are found in normal melanocytes and the E-cadherin to N-cadherin switch that is found in the conversion from normal melanocytes to metastatic melanoma, these two endpoints appear to be very relevant for identifying possible melanoma prevention activity. Caspase 3 induction was included as a biomarker for apoptosis. The induction of HLA-ABC expression, which is reduced during the conversion to melanoma and facilitates immune surveillance system, was also selected. The human cell assay for melanoma prevention was used to evaluate bromelain, an extract from the pineapple plant stem that is reported to have anticancer activities both in vitro and in vivo. Bromelain was tested in the assay at six half-log concentrations ranging from 0.3 to 100 μg/mL. Bromelain induced E-cadherin at all concentrations evaluated. N-cadherin was inhibited by five of the six concentrations. Caspase 3 was induced by five of six concentrations and HLA ABC was induced by two of six concentrations. The biomarker responses observed in the human cell screening assay suggest that bromelain may have the potential to prevent melanoma.
 >Supported by NCI Contract # N01-CN-15030.