Page 95 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P55

Antitumor features of dual COX-2 and 5-LOX inhibitors on melanoma and colon cancer cell
lines in vitro

1
1
Milan Marković , Jelena Erić , Robert Kuhnert , Evamarie Hey-Hawkins , Sanja Mijatović Danijela
2
2
1
Maksimović-Ivanić 1
1 Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, Department for
Immunology, Belgrade University, Belgrade, Serbia
2 Faculty of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Leipzig University, Leipzig, Germany

Background: Chronic inflammation inside brain, kidney, liver, melanoma, and colon tumors is in tight
connection with their growth and progression. In that context expression of the enzyme cyclooxygenase,
COX-2, takes a pivotal role as a link between inflammation and cancerogenesis promoting cell proliferation
at the same time. Furthermore, lipooxygenase-5 (5-LOX) also provokes cell division, and viability of many
inflammation-related cancers. Since both enzymes are linked to arachidonic acid metabolism, dual
inhibition of COX-2/5-LOX can be a promising approach in supression of tumor growth. Material and
methods: We have therefore examined the effect of the synthesized COX-2/5-LOX dual inhibitors
C₁₃H₂₅B₁₀O₂NS (U), C₁₆H₃₀B₁₀O₂S (V), and C₁₈H₂₇B₁₀IO₂S (W) on the viability of melanoma (B16-F1, B16-F10,
A375) as well as colon cancer lines (HCT116, SW480, CT26). All cells were treated in a dose-dependent
manner (dose range 100µM to 1.5µM) with each dual inhibitor. Cell viability was measured by MTT and
CV. Results: The results show that compound W was the most selective against CT26 cells with an IC50
value of 17.9µM which is an 8.7 times lower dose than on mouse peritoneal macrophages (155.7µM).
Cytofluorimetric analysis revealed that compound W slightly inhibits proliferation of CT26 cells in culture,
and causes apoptosis independent from phosphatidyl serine (PS) inversion, as well as caspase activity.
Furthermore, treatment with compound W strongly upregulates production of reactive oxygen/nitrogen
species by CT26 cells. Conclusion: Taken together, the inhibition of both enzymes COX-2 and 5-LOX in CT26
cell line leads to limited tumor cell growth, and might also have a beneficial influence on the tumor
microenvironment.
Keywords: Inflammation, cancer cells, COX-2, 5-LOX, dual inhibitor
Acknowledgements: Ministry of Education, Science and Technological development of the Republic of
Serbia No. 451-03-9/2021-14/200007 and Bilateral project with FR Germany (451-02-00127/2020-09/3).

82