Vitamin D regulation of energy metabolism in cancer

Abstract

Vitamin D exerts anti‐cancer effects in recent clinical trials and preclinical models. The actions of vitamin D are primarily mediated through its hormonal form, 1,25‐dihydroxyvitamin D (1,25(OH)2D). Previous literature describing in vitro studies has predominantly focused on the anti‐tumourigenic effects of the hormone, such as proliferation and apoptosis. However, recent evidence has identified 1,25(OH)2D as a regulator of energy metabolism in cancer cells, where requirements for specific energy sources at different stages of progression are dramatically altered. The literature suggests that 1,25(OH)2D regulates energy metabolism, including glucose, glutamine and lipid metabolism during cancer progression, as well as oxidative stress protection, as it is closely associated with energy metabolism. Mechanisms involved in energy metabolism regulation are an emerging area in which vitamin D may inhibit multiple stages of cancer progression. LINKED ARTICLES This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc

Themed issue: ‘New avenues in cancer prevention and treatment’

“…As mentioned above, cancer metastasis is a detrimental hallmark that is rarely studied in connection to nutrients or other dietary bioactive compounds (Khadge et al, 2018; Sleeman, 2018). In this themed issue of the British Journal of Pharmacology , Sheeley et al (2022) refer to cancer as a metabolic disease and review metabolic features of tumours which allow cancer cells to proliferate and spread throughout the body (Sheeley et al, 2022). Recent knowledge on one of the most biologically active nutrients, 1,25‐dihydroxyvitamin D, demonstrates its potential as an agent targeting metabolic pathways with minimal effects on surrounding tissues and whole‐body metabolism.…”

“…Recent knowledge on one of the most biologically active nutrients, 1,25‐dihydroxyvitamin D, demonstrates its potential as an agent targeting metabolic pathways with minimal effects on surrounding tissues and whole‐body metabolism. Hence, Sheeley et al (2022) propose 1,25‐dihydroxyvitamin D as an alternative approach to current therapies targeting metabolism where many off‐target effects are a limitation. Glucose, glutamine and lipid metabolism appear to be regulated by 1,25‐dihydroxyvitamin D in cancer cells, which may lead to a decrease in metabolic plasticity and energy production and thus attenuate cancer progression (Sheeley et al, 2022).…”

Vitamin D and Breast Cancer: Mechanistic Update

“…Indeed, it was rapidly established that 1,25D and a variety of synthetic VDR agonists exerted anticancer effects (including cell cycle arrest, (15) apoptosis, (16) and differentiation (17) ) in VDR-positive breast cancer cells in vitro as well as in some animal tumor models. (18)(19)(20) Other effects of 1,25D that were demonstrated in various breast cancer model systems included blockade of epithelial-mesenchymal transition (EMT), (21,22) invasion, (19) metastasis, (23)(24)(25) and energy metabolism, (25)(26)(27)(28)(29)(30) as well as induction of autophagy. (31)(32)(33)(34)(35) However, the specific mechanisms and pathways that link the 1,25D-VDR complex to the observed biological effects remain elusive and appear to be highly cell type specific based on mechanistic studies and genomic profiling as described below.…”

Preclinical Researches of Vitamin D Role in Preventing Malignant Diseased, a Systematic Review

“…Some of the studies reported promising antitumor activity, while others did not. Was reported that the application of high doses (20 IU/kg) of 1.25 OH) 2D3 combined with docetaxel and carboplatin was safe and well-tolerated [32].…”