The involvement of epithelial-to-mesenchymal transition in doxorubicin resistance: possible molecular targets

Mirzaei, Sepideh and Abadi, Asal Jalal and Gholami, Mohammad Hossein and Hashemi, Farid and Zabolian, Amirhossein and Hushmandi, Kiavash and Zarrabi, Ali and Entezari, Maliheh and Aref, Amir Reza and Khan, Haroon and Ashrafizadeh, Milad and Samarghandian, Saeed (2021) The involvement of epithelial-to-mesenchymal transition in doxorubicin resistance: possible molecular targets. European Journal of Pharmacology, 908 . ISSN 0014-2999 (Print) 1879-0712 (Online)

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Considering the fact that cancer cells can switch among various molecular pathways and mechanisms to ensure their progression, chemotherapy is no longer effective enough in cancer therapy. As an anti-tumor agent, doxorubicin (DOX) is derived from Streptomyces peucetius and can induce cytotoxicity by binding to topoisomerase enzymes to suppress DNA replication, leading to apoptosis and cell cycle arrest. However, efficacy of DOX in suppressing cancer progression is restricted by development of drug resistance. Cancer cells elevate their metastasis in triggering DOX resistance. The epithelial-to-mesenchymal transition (EMT) mechanism participates in transforming epithelial cells into mesenchymal cells that have fibroblast-like features. The EMT diminishes intercellular adhesion and enhances migration of cells that are necessary for carcinogenesis. Various oncogenic molecular pathways stimulate EMT in cancer. EMT can induce DOX resistance, and in this way, upstream mediators such as ZEB proteins, microRNAs, Twist1 and TGF-β play a significant role. Identification of molecular pathways involved in EMT regulation and DOX resistance has resulted in using gene therapy such as microRNA transfection and siRNA in overcoming chemoresistance. Furthermore, curcumin and formononetin, owing to their cytotoxicity against cancer cells, can suppress EMT in mediating DOX sensitivity. For promoting efficacy in DOX sensitivity, nanoparticles have been developed for boosting ability in EMT inhibition.
Item Type: Article
Uncontrolled Keywords: Chemoresistance; Delivery system; Doxorubicin; Epithelial-to-mesenchymal transition; Gene therapy; Metastasis
Divisions: Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Ali Zarrabi
Date Deposited: 30 Aug 2022 15:39
Last Modified: 30 Aug 2022 15:39

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