The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer

Abstract

Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression.

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms

“…In addition, the beneficial effect of EGCG on cells was further enhanced when vitamin D was taken at the same time [ 128 ]. Optimal levels of vitamin D have been shown to help prevent and regress low-grade squamous intraepithelial lesions of the cervix and reduce the risk of fibroids [ 266 ]. However, there is no clear statement of the exact mechanism.…”

Vitamin D and Its Receptors in Cervical Cancer

“…Several studies have reported that the VD-VDR signaling in cervical cancer cells can directly impact the expression of key oncogenes and tumor suppressor genes 47 , 48 . For instance, VDR activation has been shown to downregulate oncogenes like human cervical cancer oncogene-1 (HCCR-1) and upregulate tumor suppressors like p21 and p53, leading to cell cycle arrest and inhibition of cell proliferation 47 , 49 .…”

“… Synthesis and metabolism of VD 48 . VD is mostly produced by the skin under the influence of UVB radiation, although it can also be acquired through dietary sources.…”

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model

“…Finally, in the kidney, 25(OH)3 undergoes another hydroxylation to produce 1.25 dihydroxycholecalciferol (1.25(OH)D3), also known as calcitriol, a potent secosteroid hormone. This has a mechanism of action comparable with those of the steroid hormones (estradiol and progesterone) [ 5 ]. It acts through interaction with the vitamin D receptor (VDR) and the RXR (retinoid X receptor) coreceptor, which are present in more than 30 different cell types, including the epithelium of the female reproductive tract [ 6 ].…”