Potential Molecular Mechanisms of the Anti-cancer Activity of Vitamin D

Skrajnowska, Dorota; Bobrowska-Korczak, Barbara

doi:10.21873/anticanres.13478

Cited by 31 publications

(28 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, evidence from preclinical and clinical studies has suggested that vitamin D supplementation may decrease the risk of many cancers 9 .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Huang

Zhang

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

show abstract

“…In recent years, evidence from preclinical and clinical studies has suggested that vitamin D supplementation may decrease the risk of many cancers 9 .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Huang

Zhang

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Therefore, it is possible that vitamin D may improve survival time in patients with undifferentiated, but not differentiated carcinoma. In-vitro experiments [2,3,4] have shown the potential for vitamin D to induce differentiation of undifferentiated cancer cells in vivo. In fact, a clinical pilot trial indicated that vitamin D may increase differentiation in the normal colorectal mucosa of patients with colorectal adenoma [22], although that trial did not include patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The 25(OH)D is further activated in the kidneys by 1-alpha-hydroxylase to 1,25-dihydroxyvitamin D, which facilitates calcium absorption and plays an important role in bone health. A more recent discovery that most tissues, as well as cancers, have 1-alpha-hydroxylase to convert serum 25(OH)D to 1,25(OH)2D, along with vitamin D receptors, which are steroid hormone nuclear receptors that regulate a variety of genes within a cell [1], has provided new insights into the function of vitamin D. In particular, vitamin D has been demonstrated to induce differentiation of cancer cells in vitro [2,3,4], which leads to the hypothesis that vitamin D supplementation may improve prognosis of patients with poorly differentiated carcinoma in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Vitamin D has been repeatedly shown to induce differentiation of immature cancer cells in vitro [2,3,4]. In contrast, to the best of our knowledge, vitamin D has not been assessed in terms of its effects by maturity levels of carcinoma, e.g., well, moderately, and poorly differentiated carcinoma through examining pathological specimen derived from patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

et al. 2019

View full text Add to dashboard Cite

Some coauthors of this study previously performed the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D supplementation (2,000 IU/day) in 417 patients with stage I to III digestive tract cancer from the esophagus to the rectum who underwent curative surgery (UMIN000001977). We conducted a post-hoc analysis of the AMATERASU trial to explore the effects of modification of vitamin D supplementation by histopathological characteristics on survival. Among patients with poorly differentiated adenocarcinoma, the 5-year relapse-free survival rate of patients supplemented with vitamin D was 91% compared with 63% in the placebo group (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; P = 0.017; P for interaction = 0.023). Similarly, the 5-year overall survival rate was 92% in the vitamin D group compared with 72% in the placebo group (HR, 0.25; 95%CI, 0.07 to 0.94; P = 0.040; P for interaction = 0.012). In contrast, there were no significant effects in other histopathological characteristics between vitamin D and placebo groups. These findings generated the hypothesis that oral vitamin D supplementation may improve both relapse-free survival and overall survival in a subgroup of patients with poorly differentiated adenocarcinoma.

show abstract

“…It is activated in the skin through sun exposure, promotes the absorption of calcium and phosphorus in the intestine and maintains an adequate concentration of these minerals in the circulation to allow for normal bone mineralisation (1) . Recently, many studies have reported non-skeletal actions on cell proliferation and differentiation (2) , immune regulation (3) , anti-tumour activity (4) and muscle function (5) associated with vitamin D. Additionally, since it has been suggested that vitamin D deficiency or insufficiency is associated with an increased risk of non-skeletal health conditions, including cardiovascular diseases such as elevated blood pressure (6) , diabetes mellitus (7) , obesity (8) , infections (9) and autoimmune diseases (10) , the importance of vitamin D has gained increasing attention. Also, vitamin D insufficiency is known to be associated with sexual dysfunction in apparently healthy women and with erectile dysfunction in men (11) .…”

mentioning

confidence: 99%

Association between serum vitamin D and depressive symptoms in apparently healthy male adults undergoing routine health check-ups at a single centre

Kim

Lee

Chae

et al. 2020

Public Health Nutr.

View full text Add to dashboard Cite

Objective: To determine the level of vitamin D and to identify the association between vitamin D and depressive symptoms in apparently healthy Korean male adults. Design: A retrospective study design. Among 43 513 participants between 1 March and 30 November 2018, after eliminating participants with a history of depression or vitamin D deficiency, 9058 were included. To determine the level of vitamin D, serum 25-hydroxyvitamin D [25(OH)D] was measured. To assess the level of depression, the Korean version of the Center for Epidemiologic Studies Depression Scale (CES-D) was used. Setting: South Korea. Participants: Male adults who underwent routine health check-ups. Results: The average vitamin D level was 22·31 ± 7·09 ng/ml as 25(OH)D, while the number of subjects in the vitamin D insufficiency group with a finding of <20 ng/ml was 3783 (41·8 %). The mean CES-D score in all subjects was 8·31 ± 5·97 points, and the proportion of the depressive symptoms group with a score of ≥16 was 8·71 %. The OR of patients in the depressive symptoms group also being in the insufficiency group was found to be 1·49 (95 % CI 1·12, 2·00). Conclusions: A total of 41·8 % of apparently healthy male adults had vitamin D levels <20 ng/ml. We identified an association between vitamin D insufficiency and depressive symptoms in apparently healthy Korean male adults.

show abstract

Potential Molecular Mechanisms of the Anti-cancer Activity of Vitamin D

Cited by 31 publications

References 122 publications

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Association between serum vitamin D and depressive symptoms in apparently healthy male adults undergoing routine health check-ups at a single centre

Contact Info

Product

Resources

About