In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 2 ( 2023-2-14), p. e1010629-
Abstract:
Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010629
DOI:
10.1371/journal.pgen.1010629.g001
DOI:
10.1371/journal.pgen.1010629.g002
DOI:
10.1371/journal.pgen.1010629.g003
DOI:
10.1371/journal.pgen.1010629.g004
DOI:
10.1371/journal.pgen.1010629.g005
DOI:
10.1371/journal.pgen.1010629.g006
DOI:
10.1371/journal.pgen.1010629.s001
DOI:
10.1371/journal.pgen.1010629.s002
DOI:
10.1371/journal.pgen.1010629.s003
DOI:
10.1371/journal.pgen.1010629.s004
DOI:
10.1371/journal.pgen.1010629.s005
DOI:
10.1371/journal.pgen.1010629.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
Permalink