Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 to

Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and
LY294002 toward Human Glioma Cells In Vitro
    1 of 1     Export Download More... International Journal of Molecular SciencesVolume 25, Issue 2, January
2024, Article number 759
Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and
LY294002 toward Human Glioma Cells In Vitro(Article)(Open Access)
    Sumorek-Wiadro, J., Zając, A., Skalicka-Woźniak, K., Rzeski, W.,
Jakubowicz-Gil, J. View Correspondence (jump link)     aDepartment of Functional Anatomy and Cytobiology, Institute of
Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19,
Lublin, 20-033, Poland
    bIndependent Laboratory of Natural Products Chemistry, Medical
University of Lublin, Chodźki 1, Lublin, 20-093, Poland
    cDepartment of Medical Biology, Institute of Rural Health,
Jaczewskiego 2, Lublin, 20-950, Poland
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Furanocoumarins are naturally occurring compounds in the plant world,
characterized by low molecular weight, simple chemical structure, and
high solubility in most organic solvents. Additionally, they have a
broad spectrum of activity, and their properties depend on the location
and type of attached substituents. Therefore, the aim of our study was
to investigate the anticancer activity of furanocoumarins (imperatorin,
isoimperatorin, bergapten, and xanthotoxin) in relation to human
glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cell
lines. The tested compounds were used for the first time in combination
with LY294002 (PI3K inhibitor) and sorafenib (Raf inhibitor). Apoptosis,
autophagy, and necrosis were identified microscopically after straining
with Hoechst 33342, acridine orange, and propidium iodide, respectively.
The levels of caspase 3 and Beclin 1 were estimated by immunoblotting
and for the blocking of Raf and PI3K kinases, the transfection with
specific siRNA was used. The scratch test was used to assess the
migration potential of glioma cells. Our studies showed that the
anticancer activity of furanocoumarins strictly depended on the
presence, type, and location of substituents. The obtained results
suggest that achieving higher pro-apoptotic activity is determined by
the presence of an isoprenyl moiety at the C8 position of the coumarin
skeleton. In both anaplastic astrocytoma and glioblastoma, imperatorin
was the most effective in induction apoptosis. Furthermore, the usage of
imperatorin, alone and in combination with sorafenib or LY294002,
decreased the migratory potential of MOGGCCM and T98G cells. © 2024 by
the authors.