XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
32.
MOLECULar MECHaNISMS INvOLvED IN POTENT PLaTINUM (IV)
COMPLEX-MEDIaTED COLON caNCEr CELL SENSITIZaTION TO TraIL-
INDUCED aPOPTOSIS
Iva Jelínková 1,2 , Olga Vondálová Blanářová 1,2 , Jiřina Hofmanová 1,2 , Petr Sova 3 ,
Alois Kozubík 1,2 and Vaculová Alena 1,2
1
Department of Cytokinetics, Institute of Biophysics, AS CR, v.v.i., Brno; 2 Faculty of
Science, Masaryk University Brno; 3 R&D, Pliva-Lachema, a.s., Brno, Czech Republic
Platinum (II) complexes such as cisplatin are used in the therapy of many solid cancers,
but their application is limited due to serious side effects and/or cancer cell resistance.
Recently, platinum (IV) adamantylamine ligand-containing complex LA-12 has been introduced
and shown as highly effective in many cancer cells including colon. TRAIL (TNFrelated
apoptosis inducing ligand), a cytokine that belongs to the TNF family, is a potent
and promising anticancer agent that triggers apoptosis in many cancer but not in most
normal cells. However, some cancer cells are resistant to its effects. We demonstrated
that LA-12 was very effective in potentiation of TRAIL-induced apoptosis in colon cancer
cells. Molecular mechanisms involved in cell sensitization were investigated, with a particular
focus on the death receptors, caspases, and mitochondria. We demonstrated that
LA-12 was responsible for significant up-regulation of surface and total TRAIL receptor
2 (DR5) protein level. Combined treatment of colon cancer with both agents resulted in
enhanced caspase activation, and mitochondrial apoptotic pathway engagement. Our
results showed that LA-12 is a very promising agent to be used in combined cancer therapy
with TRAIL, and suggested the intracellular targets for the therapeutic interventions.
Acknowledgements: This work was supported by grants No. 1QS500040507 IGA AS CR
and 301/07/1557 GACR.
150 XXII. Biochemistry Congress, Martin