Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in Therapeutic Implication of Cancers

Snigdha Banerjee
* ORCID logo ,
Affan A Ansari
ORCID logo ,
Sunil P. Upadhyay
ORCID logo ,
Daniel J Mettman
ORCID logo ,
Jamie R Hibdon
,
Mohiuddin Quadir
ORCID logo ,
Pratyusha Ghosh
,
Anjali Kambhampati
,
Sushanta K Banerjee
* ORCID logo
Version 1 : Received: 25 January 2024 / Approved: 26 January 2024 / Online: 26 January 2024 (11:39:36 CET)

A peer-reviewed article of this Preprint also exists.

Banerjee, S.; Ansari, A.A.; Upadhyay, S.P.; Mettman, D.J.; Hibdon, J.R.; Quadir, M.; Ghosh, P.; Kambhampati, A.; Banerjee, S.K. Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers. Cells 2024, 13, 395. Banerjee, S.; Ansari, A.A.; Upadhyay, S.P.; Mettman, D.J.; Hibdon, J.R.; Quadir, M.; Ghosh, P.; Kambhampati, A.; Banerjee, S.K. Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers. Cells 2024, 13, 395.

Abstract

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleo-side antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with inhibition of cancer cell growth and progression of tumors. Thus, TM can be considered a potent antitumor drug in various cancers and may promote chemosensitivity. Mechanistically, TM impedes the role of the UDP-HexNAc enzyme in the biosynthesis of oligosaccharides, specialized macromolecules instrumental in N-linked glycosylation. Further, like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and Cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Despite TM's antitumor effectiveness, its lack of cell-type specific cytotoxicity impedes its anticancer efficacy. Thus, various nanoencapsulation techniques and materials have been considered for use in experiments to reduce TM's cytotoxicity and improve efficacy as a targeted therapy. The current review is a profound audit of the benefits and pitfalls of TM in various cancers, focusing on breast, colon, and pancreatic cancers. Additional progressive studies have also discussed the use of TM in immune checkpoints and other unique pathways. Cytotoxicity and other possibly adverse effects of TM are highlighted based on the data from in vitro and in vivo assays. In addition, the recent advances in nano-based drug delivery systems regarding TM have been emphasized. However, the potential of this nucleoside inhibitor re-quires thorough investigation and research to determine its likeliness as a viable chemotherapeutic.

Keywords

Tunicamycin; Nanoparticle; Immunotherapy; Glycosylation; Drug resistance; Multidrug therapy; cancer

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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