New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities
Ashrafizadeh, Milad Mirzaei, Sepideh Hashemi, Farid Zarrabi, Ali Zabolian, Amirhossein Saleki, Hossein Sharifzadeh, Seyed Omid Soleymani, Leyla Daneshi, Salman Hushmandi, Kiavash
Ashrafizadeh, Milad
Mirzaei, Sepideh
Hashemi, Farid
Zarrabi, Ali
Zabolian, Amirhossein
Saleki, Hossein
Sharifzadeh, Seyed Omid
Soleymani, Leyla
Daneshi, Salman
Hushmandi, Kiavash
Citations
Altmetric:
Alternative Title
Abstract
Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis and migration of cancer cells to neighboring cells and tissues. Morphologically, epithelial cells are transformed to mesenchymal cells, and at molecular level, E-cadherin undergoes down-regulation, while an increase occurs in N-cadherin and vimentin levels. Increasing evidence demonstrates role of EMT in mediating drug resistance of cancer cells. On the other hand, paclitaxel (PTX) and docetaxel (DTX) are two chemotherapeutic agents belonging to taxene family, capable of inducing cell cycle arrest in cancer cells via preventing microtubule depolymerization. Aggressive behavior of cancer cells resulted from EMT-mediated metastasis can lead to PTX and DTX resistance. Upstream mediators of EMT such as ZEB1/2, TGF-?, microRNAs, and so on are involved in regulating response of cancer cells to PTX and DTX. Tumor-suppressing factors inhibit EMT to promote PTX and DTX sensitivity of cancer cells. Furthermore, three different strategies including using anti-tumor compounds, gene therapy and delivery systems have been developed for suppressing EMT, and enhancing cytotoxicity of PTX and DTX against cancer cells that are mechanistically discussed in the current review. © 2021
Keywords
Chemoresistance, Docetaxel, Drug resistance, Epithelial-to-mesenchymal transition (EMT), Metastasis, Paclitaxel
Source Title
Biomedicine and Pharmacotherapy
Publisher
Elsevier Masson s.r.l.
Series/Report No.
Collections
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Date
2021-09-01
DOI
10.1016/j.biopha.2021.111824
Type
Review