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Radziejewska 1, *, Katarzyna Supruniuk 2, Katarzyna Jakimiuk 3, Michał Tomczyk 3, Anna Bielawska 4 and Anna Galicka 1  \nCitation: Radziejewska, I.;  \nSupruniuk, K.; Jakimiuk, K.; Tomczyk, M.; Bielawska, A.; Galicka, A. Tiliroside Combined with  \nAnti-MUC1 Monoclonal Antibody as Promising Anti-Cancer Strategy in AGS Cancer Cells. Int. J. Mol. Sci. 2023, 24, 13036. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms241713036](10.3390/ijms241713036)  \nAcademic Editors: Antonio Carrillo-Vico and Ivan Cruz-Chamorro  \nReceived: 7 July 2023  \nRevised: 27 July 2023  \nAccepted: 17 August 2023  \nPublished: 22 August 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Medical Chemistry, Medical University of Białystok, ul. Mickiewicza 2a, 15-222 Białystok, Poland; [anna.galicka@umb.edu.pl](anna.galicka@umb.edu.pl)  \n2 Department of Medical Biology and Genetics, Medical University of Gda ´nsk, ul. D˛ebinki 1, 80-211 Gda ´nsk, Poland; [katarzyna.supruniuk@gumed.edu.pl](katarzyna.supruniuk@gumed.edu.pl)  \n3 Department of Pharmacognosy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Białystok, ul. Mickiewicza 2a, 15-230 Białystok, Poland; [katarzyna.jakimiuk@umb.edu.pl](katarzyna.jakimiuk@umb.edu.pl) (K.J.); [michal.tomczyk@umb.edu.pl](michal.tomczyk@umb.edu.pl) (M.T.)  \n4 Department of Biotechnology, Medical University of Białystok, ul. Kili ´nskiego 1, 15-089 Białystok, Poland; [aniabiel@umb.edu.pl](aniabiel@umb.edu.pl)  \n* Correspondence: [iwona@umb.edu.pl](iwona@umb.edu.pl); Tel.: +48-85-535-934-079  \nAbstract: Speciﬁc changes in mucin-type O-glycosylation are common for many cancers, including gastric ones. The most typical alterations include incomplete synthesis of glycan structures, enhanced expression of truncated O-glycans (Tn, T antigens and their sialylated forms), and overexpression offucosylation. Such altered glycans inﬂuence many cellular activities promoting cancer development. Tiliroside is a glycosidic dietary ﬂavonoid with pharmacological properties, including anti-cancer. In this study, we aim to assess the effect of the combined action of anti-MUC1 and tiliroside on some cancer-related factors in AGS gastric cancer cells. Cancer cells were treated with 40, 80, and 160 􀀖M tiliroside, 5 􀀖g/mL anti-MUC1, and ﬂavonoid together with mAb. Real-Time PCR, ELISA, and Western blotting were applied to examine MUC1 expression, speciﬁc, tumor-associated antigens, enzymes taking part in their formation, Gal-3, Akt, and NF-􀀔B. MUC1 expression was signiﬁcantly reduced by mAb action. The combined action of anti-MUC1 and tiliroside was more effective in comparison with monotherapy in the case of C1GalT1, ST3GalT1, FUT4, Gal-3, NF-􀀔B, Akt mRNAs, and Tn antigen, as well as sialyl T antigen expression. The results of our study indicate that applied combined therapy may be a promising anti-gastric cancer strategy.  \nKeywords: tiliroside; gastric cancer; glycoforms; MUC1; TACAs  \n1. Introduction  \nGastric cancer (GC) is stated to be the ﬁfth most common cancer and the third most frequent cause of cancer deaths worldwide [1] . Surgery still remains the main treatment for early-diagnosed, operable patients. For advanced GC, new therapeutic methods are currently being studied [2] .  \nIt is reported that many natural plant-based chemical compounds possess anti-cancer properties. They are able to impair and even kill cancer cells without being toxic to healthy cells [3–5] . The main group of such compounds is polyphenols, widely distributed in","cbCait5FH7BAEbD7","https://ap.wps.com/l/cbCait5FH7BAEbD7","pdf",3575598,16,"English","# Abstract\n# Introduction","[{\"question\":\"What cancer-related glycosylation changes are highlighted as common in tumors?\",\"answer\":\"The text emphasizes mucin-type O-glycosylation changes, including incomplete glycan synthesis, increased truncated O-glycans (Tn/T antigens and sialylated forms), and enhanced fucosylation-related expression.\"},{\"question\":\"What is the goal of combining anti-MUC1 with tiliroside in AGS cells?\",\"answer\":\"The study aims to assess the combined effect on cancer-related factors in AGS gastric cancer cells, focusing on MUC1-related signaling and tumor-associated targets.\"},{\"question\":\"How did the combined therapy compare with monotherapy?\",\"answer\":\"The combined action of anti-MUC1 and tiliroside was more effective than monotherapy for multiple targets, including C1GalT1, ST3GalT1, FUT4, Gal-3, NF-κB, Akt mRNAs, and Tn antigen, as well as sialyl T antigen expression.\"}]","Tiliroside Combined with Anti-MUC1 Monoclonal Antibody as Promising Anti-Cancer Strategy in AGS Cancer Cells | PDF",1790228923]