Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2017.58.129
4-Thiazolidinone derivative Les-3833 effectively inhibits viability of human melanoma cells through activating apoptotic mechanisms
Nataliya Finiuk
; Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Nataliya Boiko
; Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Olga Klyuchivska
; Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Lesya Коbylinska
; Department of Biochemistry Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Iryna Kril
; Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Borys Zimenkovsky
; Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Roman Lesyk
; Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Rostyslav Stoika
; Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology, National Academy of Sciences of Ukraine Lviv, Ukraine
Sažetak
Aim To evaluate cytotoxic action of 4-thiazolidinone derivative
Les-3833 and study the mechanisms of its pro-apoptotic
action toward human melanoma cells and human tumor
cell lines of other tissue origin.
Methods The effect of Les-3833 or doxorubicin on the viability
of 9 cell lines was studied using MTT assay, while
human melanoma cells of WM793 line were additionally
examined using light and fluorescent microscopies for
evaluating cytomorphological changes. The Western-blot
and flow cytometric analyses were carried out to study signaling
pathways of melanoma cell cycling and death.
Results Les-3833 was the most efficient against melanoma
cells. Its half maximal inhibitory concentration (IC50)
was 0.22 μg/mL for WM793 cells and 0.3 μg/mL for SK-Mel-
28 melanoma cells. For human lung A549, breast MCF-7,
colon HCT116, and ovarian SKOV3 carcinoma cell lines IC50
was in between 2.5 to >5.0 μg/mL. Les-3833 was relatively
not toxic (IC50 > 5 μg/mL) for human embryonic kidney
HEK293 cells. Results of Annexin V/PI staining of melanoma
cells and activation of caspase 3, PARP, MAPK, and EndoG
protein suggest apoptosis in Les-3833-treated cells. Les-
3833 also induced ROS production in melanoma cells and
their arrest in G0/G1 phase of cell cycle.
Conclusion Novel 4-thiazolidinone derivative Les-3833 is
effective against human melanoma cells in vitro, and such
effect is tumor specific since it is much less pronounced in
human carcinoma and leukemia cells. In melanoma cells
Les-3833 induces apoptosis (morphological changes and
increased pro-apoptotic proteins), ROS production, and arrest
in G0/G1 phase of cell cycle.
Ključne riječi
Hrčak ID:
181595
URI
Datum izdavanja:
15.4.2017.
Posjeta: 966 *