Hypoxia—a characteristic of almost all types of solid tumors—has been associated with poor outcomes in several human malignancies. Genipin—an active constituent of Gardenia fruit— has been reported to exert an anti-tumor effect in several cancers. In this study, we investigated inhibition of angiogenesis using Genipin-mediated hypoxia-induced hypoxia inducible factor (HIF-1) and VEGF expression in human cervical cancer cells.

Under normoxic and hypoxic conditions, the expression of HIF-1α and VEGF in cervical cancer HeLa cells was detected by quantitative reverse transcription polymerase chain reaction and western blotting. Luciferase reporter assays were used to investigate the molecular mechanisms underlying the hypoxia-induced survivin activation.

Surprisingly, we found that Genipin suppressed the HIF-1α accumulation during hypoxia in human liver cancer cell line (HepG2), human prostate cancer cell line (LNCaP), colon cancer cell line (HCT116), and breast cancer cell line (MDA231). Genipin treatment also significantly reduced hypoxia-induced secretion of VEGF.

Suppression of HIF-1α accumulation following treatment with Genipin under hypoxia was associated with PI3K and MAPK pathways. Taken together, these results suggested that Genipin inhibits HIF-1α expression through inhibition of PI3K and MAPK signaling pathways. These results provide new insights into a potential mechanism of the anticancer properties of Genipin.

Nowadays most infants on exclusively breast feeding have vitamin D deficiency due to the increase of breast feeding. However, domestic research lacks appropriate materials. Therefore, we researched practical clinical aspects of vitamin D deficiency related to breast milk feeding for infants who have a high amount of alkaline phosphatase (> 500 IU/L).

The subjects of the study were 31 infants with high alkaline phosphatase level. We tested with 25-hydroxycholecalciferol (25-OHD₃), parathyroid hormone, calcium, ionized calcium, phosphorus in their blood and with a wrist x-ray. Then, we divided them into two groups of breast feeding and formula feeding and compared the results.

Eighteen infants (58%) out of 31 infants that have high alkaline phosphatase were vitamin D insufficiency or deficiency, and 16 (100%) breast feeding infants of them showed vitamin D deficiency or insufficiency. However, only 2 (13%) of 15 formula feeding infants were at insufficiency. There was a correlation between alkaline phosphatase and 25-OHD₃ concentration in multiple regression analysis, but no correlation in other variables was found in group of breast milk feeding infants. There was neither correlation between vitamin D concentration and alkaline phosphatase nor other correlated variables in the group of formula milk feeding infants.

In this study, there was a high probability of vitamin D deficiency in the breast feeding infants with a high alkaline phosphatase level. Therefore, it is considered to be worth utilizing alkaline phosphatase as a screening test for vitamin D deficiency or rickets for breast feeding infants.