Anti-cancer effect of combined action of anti-MUC1 and rosmarinic acid in AGS gastric cancer cells

Abstract

MUC1 seems to be promising target in cancer cells due to its abundant and specifically altered expression as well as differential distribution pattern relative to normal tissues. Rosmarinic acid (RA) is a natural, polyphenolic compound with pharmacological activities, including anti-cancer. Herein, we aim to explore the effect of combined action of anti-MUC1 and RA on selected cancer-related factors in AGS gastric cancer cells.Cancer cells were treated with 100, 200 μM rosmarinic acid, 5 μg/ml anti-MUC1 and acid together with antibody. Western blotting, ELISA and RT-PCR were used to assess the expression of MUC1, selected sugar antigens, enzymes participating in protein glycosylation, Gal-3, p53, pro- and anti-apoptotic factors, and caspases-3,-8,-9 in cancer cells.MUC1 mRNA was significantly suppressed by combined action of anti-MUC1 and RA. Such treatment markedly inhibited expression of cancer-related Tn, T, sialyl Tn, sialyl T, and fucosylated sugar antigens as well as mRNA expression of enzymes participating in their formation: ppGalNAcT2, C1GalT1, ST6GalNAcT2, ST3GalT1 and FUT4. C1GalT1 was suppressed also on protein level. Gal-3, factor likely participating in metastasis, was significantly suppressed on mRNA level by RA administrated with anti-MUC1. Pro-apoptotic Bax protein and Bad mRNA were significantly induced, and anti-apoptotic Bcl-2 mRNA expression was inhibited by such treatment. Combined action of mAb and RA markedly increased caspase-9 mRNA expression.Results of the study indicate that combined action of anti-MUC1 and RA is more effective than monotherapy in relation to examined cancer related factors. Such treatment can be considered as new, promising strategy in gastric cancer therapy.