Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells

Abstract

Background Melanoma is one of the most aggressive types of cancer and it has shown a remarkable surge in incidence during the last 50 years. Melanoma has been projected to be continuously rising in the future. Therapy for advanced-type melanoma is still a challenge due to the low response rate and poor 10-year survival. Interestingly, several epidemiological and preclinical studies had reported that vitamin D deficiency was associated with disease progression in several cancer types. In vivo and in vitro studies revealed anti-proliferative, anti-angiogenic, apoptosis, and differentiation induction effects of calcitriol in various cancers. However, information on the effects of calcitriol (1,25(OH) 2 D 3 ) on melanoma is still limited, and its mechanism remains unclear. Material/Methods In the present study, by utilizing B16–F10 cells, which is a melanoma cell line, we explored the anti-proliferative effect of calcitriol using cell viability assay, near-infrared imaging, expression of apoptosis-related genes using real-time polymerase chain reactions (PCR), and the expression of apoptosis proteins levels using western blot. In addition, we also assessed calcitriol uptake by B16–F10 cells using high-performance liquid chromatography (HPLC). Results We found that calcitriol inhibits melanoma cell proliferation with an IC 50 of 93.88 ppm (0.24 μM), as shown by cell viability assay. Additionally, we showed that B16–F10 cells are capable of calcitriol uptake, with a peak uptake time at 60 min after administration. Calcitriol was also able to induce apoptosis-related proteins such as caspase-3, caspase 8, and caspase-9. These effects of calcitriol reflect its potential utility as a potent adjuvant therapy for melanoma. Conclusions Calcitriol inhibits cell proliferation and induces apoptosis in B16–F10 cells.

In Vivo and In Vitro Evidence for an Interplay between the Glucocorticoid Receptor and the Vitamin D Receptor Signaling

“…Calcitriol modulates apoptosis in different ways, notably by enhancing the cell death of abnormal cells and by decreasing the apoptosis of healthy cells. For instance, calcitriol strongly affects the viability of several cancer cell lines, whereas calcitriol protects β-cells against high glucose-induced apoptosis [ 39 , 40 , 41 ]. In the context of EAE, calcitriol has been shown to enhance the sensitivity of pathogenic T cells to apoptosis in vivo by increasing the level of pro-apoptotic genes and decreasing the level of anti-apoptotic genes [ 42 , 43 ].…”

The Chemoprotective Role of Vitamin D in Skin Cancer: A Systematic Review

“…31 Furthermore, this high level of VDR was found in less aggressive cancer cells and correlated with a good prognosis. 32 In the in vitro preclinical studies, [13][14][15][16][17][18][19][20][21] most of the samples were melanoma cell lines, either from humans or animals (mice). Most of these in vitro studies concluded that vitamin D derivatives, one of which was calcitriol, could increase the inhibition of melanoma cell proliferation, thereby reducing the growth of these tumor cells.…”

“…Five studies investigated melanoma cell lines, two studied malignant-type melanoma cells, and another two investigated hamster cell lines. Only a study by 2022 13 In vitro…”

The role of fat‐soluble vitamins in efferocytosis

“…39 Caspases 3, 8, and 9 can all be activated by calcitriol. 51 Caspases are necessary for all efferocytosis phases (Find-Me, Eat-Me signals, engulfment, and anti-inflammatory responses). Thus, by controlling efferocytosis, caspase-dependent cellular processes may be related to cancer.…”

“…Vitamin D and calcium may lower the incidence of colorectal cancer, at least in part, by increasing apoptotic levels in the colon 39 . Caspases 3, 8, and 9 can all be activated by calcitriol 51 . Caspases are necessary for all efferocytosis phases (Find‐Me, Eat‐Me signals, engulfment, and anti‐inflammatory responses).…”