Open AccessJLK1486, a N , N ‐[(8‐hydroxyquinoline)methyl]‐substituted benzylamine analogue, inhibits melanoma proliferation and induces autophagy
Author(s) -
Koekemoer T. C.,
Venter M.,
Kraus J.L.
Publication year - 2014
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12127
Subject(s) - acridine orange , autophagy , mtt assay , cell growth , chemistry , viability assay , cell cycle , apoptosis , vacuole , melanoma , trypan blue , population , microbiology and biotechnology , cell , biology , cancer research , biochemistry , medicine , cytoplasm , environmental health
Objectives To investigate anti‐proliferatory activity of a selected N , N ‐[(8‐hydroxyquinoline)methyl]‐substituted benzylamine (JLK1486) on melanoma cells and to characterize its mechanism of cell population growth inhibition. Materials and methods In vitro cultures of B16F10 (mouse melanoma) cells were used as a model to characterize anti‐proliferatory activity of JLK 1486 using MTT growth assay, trypan blue viability assessment, cell cycle analysis, melanin production, β‐galactosidase and acridine orange staining. Results Proliferating B16F10 and also MeWo (human melanoma) cells were strongly growth inhibited by JLK 1486, displaying IC 50 values of 196 n m and 110 n m respectively. Anti‐proliferatory effects were independent of cell death and were characterized by a distinct accumulation of cells in G 0 /G 1 phase. Tyrosinase activity and relative melanin content remained unchanged indicating that the anti‐proliferatory activity was not due to phenotype differentiation. Although treated B16F10 cells stained strongly positive for senescence marker β‐galactosidase, cells regained near normal proliferatory activity after removal of JLK 1486. Increased acridine orange staining and presence of perinuclear vacuoles suggested induction of autophagy in B16F10 cells. Furthermore, JLK 1486 pre‐treatment completely abolished melphalan and antimycin A‐induced apoptosis. Conclusion JLK1486 provides a promising chemical scaffold to develop new anti‐melanoma drugs or combination therapies, due to its potent inhibition of cell proliferation and induction of autophagy, at pharmacologically relevant concentrations.