Vitamin D 3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells

Santos, Julianna; Khan, Zeina S.; Munir, Maliha Tabassum; Tarafdar, Kaiser; Rahman, Shaikh Mizanoor; Hussain, Fazle

doi:10.1016/j.jnutbio.2017.10.013

Cited by 45 publications

(38 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lactate production also increased consistently after VDR knockdown in MEG3-overexpressed cells (Figure 6B). Previous studies have shown that vitamin D decreases glycolysis in various cancers, including CRC (23)(24)(25). We speculated whether MEG3 mediated vitamin D-induced inhibition of glycolysis.…”

Section: Vitamin D Receptor Knockdown Abolishes the Effect Of Meg3 Onmentioning

confidence: 92%

Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation

Zuo

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Colorectal cancer (CRC), a common tumor, is characterized by a high mortality rate. Long non-coding RNA maternally expressed gene 3 (MEG3) serves a regulatory role in the carcinogenesis and progression of several types of cancer; however, its role in CRC remains largely unknown. The aim of this study was to explore the regulatory role and mechanism(s) of MEG3 in CRC. The Warburg effect or aerobic glycolysis is characteristic of the metabolism of tumor cells. To determine the effect of MEG3 on glycolysis of CRC cells, we used an XF analyzer to perform glycolysis stress test assays and found that overexpression of MEG3 significantly inhibited glycolysis, glycolytic capacity, as well as lactate production in CRC cells, whereas knockdown of MEG3 produced the opposite effect. Mechanistically, overexpression of MEG3 induced ubiquitin-dependent degradation of c-Myc and inhibited c-Myc target genes involved in the glycolysis pathway such as lactate dehydrogenase A, pyruvate kinase muscle 2, and hexokinase 2. Moreover, we found that MEG3 can be activated by vitamin D and vitamin D receptor (VDR). Clinical data demonstrated that MEG3 was positively associated with serum vitamin D concentrations in patients with CRC. We found that 1,25(OH) 2 D 3 treatment increased MEG3 expression, and knockdown of VDR abolished the effect of MEG3 on glycolysis. These results indicate that vitamin D-activated MEG3 suppresses aerobic glycolysis in CRC cells via degradation of c-Myc. Thus, vitamin D may have therapeutic value in the treatment of CRC.

show abstract

Section: Vitamin D Receptor Knockdown Abolishes the Effect Of Meg3 Onmentioning

confidence: 92%

Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation

Zuo

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…(192)(193)(194)(195) For highly glycolytic cancer cells, this inhibition of glucose metabolism is detrimental, resulting in loss of proliferation and increased apoptosis. (193,195,196) In several studies, this decrease in glycolysis is linked to inhibition of c-Myc, a regulator of glycolytic gene transcription, by 1,25D. (192,195,196) It has also been reported that 1,25D is able to suppress glutamine metabolism in breast cancer cells, partially through inhibiting transcription of the glutamine transporter.…”

Section: Cellular Metabolismmentioning

confidence: 99%

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

et al. 2020

View full text Add to dashboard Cite

Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic Tregulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

show abstract

“…Although its positive effects have been shown, not much is known as to the mechanisms involved. Santos et al [163] tested the effect of VD3 on MCF-7 and MDA-MB-231 cells. VD3 significantly reduced GLUT1 mRNA and protein levels and glucose uptake in both cell types.…”

Section: Benzyl Isothiocyanate (Bitc)mentioning

confidence: 99%

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Barbosa

Martel

2020

Cancers

View full text Add to dashboard Cite

Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation. Herein we review the compounds, both of natural and synthetic origin, found to interfere with uptake of glucose by breast cancer cells, and the consequences of interference with that mechanism on breast cancer cell biology. We will also present data where the interaction with GLUT is exploited in order to increase the efficiency or selectivity of anticancer agents, in breast cancer cells.

show abstract

Vitamin D 3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells

Cited by 45 publications

References 56 publications

Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation

Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Contact Info

Product

Resources

About