Abstract
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
SK-MEL-2 cells were stimulated at 43 °C for 1 h and treated with 0, 0.1 and 1 μM 17-DMAG.
We evaluated the cell viability using MTT and apoptosis with HSP 90 inhibitor. We
studied the protein expression of AKT, phospho-AKT, ERK, 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 °C (0.1 μM:
44.47% and 1 μM: 61.23%) and 43 °C (0.1 μM: 49.21% and 1 μM: 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 μM) and 3.05% (1 μM) in 37 °C controls,
and 4.40% (0.1 μM) and 4.97% (1 μM) in the group stimulated at 43 °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.
Keywords
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Article info
Publication history
Published online: February 08, 2018
Received:
September 6,
2017
Identification
Copyright
© 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
