Vitamin C-induced competitive binding of HIF-1α and p53 to ubiquitin E3 ligase CBL contributes to anti-breast cancer progression through p53 deacetylation. (October 2022)

• Record Type: Journal Article
• Authors: Xiong, Yan; Xu, Shiyao; Fu, Beibei; Tang, Wanyan; Zaky, Mohamed Y.; Tian, Rong; Yao, Rui; Zhang, Shanfu; Zhao, Qingting; Nian, Weiqi; Lin, Xiaoyuan; Wu, Haibo
• Is Part Of: Food and chemical toxicology. Volume 168(2022)
• Publication Date: 2022-10
• Subjects: HIF-1α -- p53 -- Acetylation -- SIRT1 -- Vitamin C; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.113321
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Vitamin C (VC), in regard to its effectiveness against tumors, has had a controversial history in cancer treatment. However, the anticancer mechanisms of VC are not fully understood. Here, we reported that VC exerted an anticancer effect on cancer cell and xenograft models via inhibiting HIF-1α-dependent cell proliferation and promoting p53-dependent cell apoptosis. To be specific, VC modulated the competitive binding of HIF-1α and p53 to their common E3 ubiquitin ligase CBL, thereby inhibiting tumorigenesis. Moreover, VC treatment activated SIRT1, resulting in p53 deacetylation and CBL-p53 complex dissociation, which in turn facilitated CBL recruitment of HIF-1α for ubiquitination in a proteasome-dependent manner. Altogether, our results provided a mechanistic rationale for exploring the therapeutic use of VC in cancer therapy.