Heat shock protein 90 inhibitor enhances apoptosis by inhibiting the ART pathway in thermal-stimulated SK-MEL-2 human melanoma cell line

Background: Heat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence. Objective: We evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions. Methods: SIC-MEL-2 cells were stimulated at 43 degrees C for 1 h and treated with 0, 0.1 and 1 mu M 17-DMAG. We evaluated the cell viability using MIT and apoptosis with HSP 90 inhibitor. We studied the protein expression of Ala, phospho-AKT, ERIC, phospho-ERK, MAPK, and phospho-MAPK, caspase 3,7,9, and anti poly (ADP-ribose) polymerase. Results: 17-DMAG significantly inhibited the proliferation of the SK-MEL-2 cells at 37 degrees C (0.1 mu M: 44.47% and 1 mu M: 61.23%) and 43 degrees C (0.1 mu M: 49.21% and mu M: 63.60%), suggesting synergism between thermal stimulation and 17-DMAG. 17-DMAG treatment increased the frequency of apoptotic cell populations to 2.17% (0.1 mu M) and 3.05% (1 mu M) in 37 degrees C controls, and 4.40% (0.1 mu M) and 4.97% (1 mu M) in the group stimulated at 43 degrees C. AKT phosphorylation were activated by thermal stimulation and inhibited by 17-DMAG. Conclusion: Hsp90 inhibitor treatment may be clinically applicable to enhance the apoptosis of melanoma cells in hyperthermic condition. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.