Synergistic antitumoral effect of combined gemcitabine with catechol-rut

MOLEJON, MI; WEIZ G; BRECCIA JD; VACCARO MI

Mar del Plata

Congreso; Reunión Anual de SOCIEDADES DE BIOCIENCIA; 2019

SAIC

Doublecortin-like kinase 1 (DCLK1) is upregulated in various cancers including pancreatic ductal adenocarcinoma (PDAC). Although the standart first-line treatment for pancreatic cancer is the use of gemcitabine alone, the resistance to this compound is common cause of therapeutic failure in this type of cancer. Combined chemotherapy with a second drug constitutes an interesting strategy to inhibit the malign cells and/or prevent the emergence of resistance. Owing to the difunctional benzene, catechol, has antitumor activity against many cancers while its effect on PDAC remains unknown. We explored the anti-cancer activity of an enzymatically glycosylated variant of the aromatic compound (catechol-rutinoside) combined with gemcitabine on the human pancreatic cancer cells (PANC-1). Interestedly, the addition of the glycosydic moiety, rutinose, significantly chemo-sensitized gemcitabine-resistant cells. We also evaluated the expression of DCLK1 in primary pancreatic tumoral cells, and found that DCLK1 expression is highly associated with gemcitabine resistance. Moreover, the effect of gemcitabine treatment combined with conjugated catechol exerted an interesting synergistic inhibitory effect on PDAC cells associated to the inhibition of the expression of DCLK1.