Impaired pentose phosphate pathway in the development of 3D MCF-7 cells mediated intracellular redox disturbance and multi-cellular resistance without drug induction

2Citations
Citations of this article
6Readers
Mendeley users who have this article in their library.

Abstract

Although metabolic reprogramming and redox imbalance are widely reported to be involved in chemo-resistance in cancer treatment, much more attention was paid to anti-cancer drug induced effect. Our previous studies showed that cancer cells can develop P-gp overexpression-mediated intrinsic drug resistance in the formation of 3D MCF-7 multi-cellular layers (MCLs) without any drug induction. However, whether metabolic reprogramming and redox imbalance functioned during this progress remained unrevealed. In our present study, LC-Q/TOF-MS and GC-MS were used in combination for analysing intracellular metabolites. The contribution of pentose phosphate pathway (PPP) and its related redox status were checked by chemical interfering and silencing/over-expression of glucose-6-phosphate dehydrogenase (G6PD). The downstream products of G6PD were assayed by quantitative real-time PCR, western blot and flow cytometry. Results showed that not only G6PD expression but also G6PD activity was significantly lowered along with 3D MCF-7 cells culture time. Impaired PPP disturbed redox-cycling, generated reactive oxygen species (ROS), which triggered cell cycle arrest and caused the switch to Chk2/p53/NF-κB pathway-mediated P-gp induction. Our results provided a new attempt to associate intrinsic small molecule metabolites (impaired PPP) communicating with cell signalling pathways through disturbed intracellular redox status to elucidate multi-cellular resistance (MCR) in 3D MCF-7 cells, which improved the understanding of the mechanisms of P-gp up-regulation in MCR with metabolomic and related redox status support.

Cite

CITATION STYLE

APA

Wang, W., Cai, Q., Zhou, F., Liu, J., Jin, X., Ni, P., … Zhang, J. (2018). Impaired pentose phosphate pathway in the development of 3D MCF-7 cells mediated intracellular redox disturbance and multi-cellular resistance without drug induction. Redox Biology, 15, 253–265. https://doi.org/10.1016/j.redox.2017.12.009

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free