Calcitriol

Endometriosis is a chronic disease that causes endometrial tissues to migrate and grow outside the uterus and is often associated with pain and infertility. The growths are estrogen-dependent but progesterone-resistant due to the lack of progesterone receptors. In the U.S., estrogen deprivation is the primary approach to treating the disease, which often leads to severe consequences such as osteoporosis and menopausal symptoms. KBU2046 is a chemical analog of genistein that has been shown to effectively inhibit the motility of prostate cancer cells with no toxicity to normal cells or estrogenic activity (Li Xu et al., 2010). This in vitro study showed that KBU2046 at 10μM significantly decreased the viability of 12Z cells to 27% and 34% at 24 hours and 48 hours posttreatment, respectively. At 48 hours post-treatment, micromolar concentrations of the combinations of KBU2046 with dienogest or calcitriol effectively decreased the viability of 12Z cells to 16% and 58.9%, respectively. KBU2046 with sodium butyrate decreased viability to 7.7%, but millimolar concentrations of the latter were required. KBU2046, in combination with calcitriol, synergistically decreased the migration and colony formation of the 12Z cells to 19.3% and 45.7%, respectively. KBU2046 and Calcitriol-treated 12Z cells are slower to the recovery of growth following treatment. KBU2046 and calcitriol decreased the secretion of PGE2 to 6.5% and 16.7%, respectively, while ethanol and the combinations of ethanol and DMSO increased the secretion of PGE2 to 83.8%, and 63.2%, respectively. In conclusion, a combination of KBU2046 and calcitriol at micromolar concentrations markedly inhibited the migration and growth of endometrial cells while decreasing the secretion of a key inflammatory molecule. In vivo studies with mouse models are needed to evaluate using a combination of KBU2046 and calcitriol for endometriosis therapy and whether millimolar plasma concentrations can be safely achieved by dietary means.

Endometriosis is an inflammatory metastatic disease that affects the endometrium of one in ten women. Endometrial tissue grows outside the uterus causing severe discomfort and pain. This disease is estrogen dependent, driving the invasion and migration of endometrial lesions to form the ectopic uterus. Due to the hormonal imbalance of increased estrogen, there is progesterone resistance leading to a decrease in progesterone receptors. This study determined if the combination of Melatonin, a naturally occurring hormone, and Calcitriol, the active form of vitamin D, had a synergistic or additive effect on the growth and migration of endometrial cells. The experiments utilized the immortalized endometriotic epithelial (12 Z) cell lines to conduct cell viability, wound closure, and clonogenic growth and growth curves. Results revealed that a combination of Melatonin and Calcitriol had an additive effect in reducing cell viability, inhibiting migration, and decreasing proliferation.

Endometriosis is an inflammatory disease that affects one in ten women, where ectopic endometrial cells grow outside of the uterus. Lesions are estrogen dependent but progesterone resistant due to decreased progesterone receptor activity. This study investigated whether a combination of dienogest, a synthetic progesterone, and calcitriol, vitamin D’s active form, had an additive or synergistic effect in the therapy of endometriosis. Experiments were conducted on immortalized endometriotic epithelial (12Z) and stromal (22B) cell lines. Results revealed that the combination therapy effectively inhibited cell viability in spheroids, limited proliferation, and reduced cell migration in cell monolayers of lipopolysaccharide- induced cells. Concentrations of prostaglandin E2, a key inflammatory cytokine, were measured from the supernatants of 12Z cells. The combination did not alter CD44 and progesterone receptor levels on the surface of 12Z cells. Further testing in a mouse model is necessary to determine the
efficacy of the combination in vivo.

Prostate cancer, the most frequent non-skin cancer, is the second leading cause of cancer-related deaths in males within the United States. Men diagnosed with metastatic prostate cancer have a 5-year survival rate of approximately 30%. Goals of this study were to produce a combination of compounds that are effective against the disease with minimal side effects on normal cells, especially those of the immune system.
This study showed KBU2046 in combination with calcitriol, limit proliferation, inhibit migration, and are cytotoxic in a testosterone dependent human prostate cancer cell line. Organic compounds, ellagic acid and curcumin were tested alone and in combination with either calcitriol or KBU2046. No combinations were as effective as KBU2046 and calcitriol in inhibiting migration and proliferation of LNCaP cells.
The findings of this study support further investigation into therapeutic use of a combination of KBU2046 and calcitriol in prevention and remission of human prostate cancer.