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.

Basal cell carcinoma (BCC) tumors are locally invasive but rarely metastatic. However, aggressive metastatic variants are being increasingly reported in elderly people. Here we investigated the clinical utility of vascular endothelial growth factor (VEGF) as a predictive biomarker for aggressive BCC variants.

Thirty-five pathologically confirmed cases of BCC that underwent surgical removal in the Plastic Surgery Department between January 1, 2011 and December 31, 2012 were studied. VEGF expression was analyzed in formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining. Positive staining was defined as more than 10% of the tumor cells showing immunoreactivity. The associations of VEGF expression with various clinicopathologic parameters were analyzed.

The face was the most prevalent site (28/35), with 15 cases from the nose, 6 cases from the eyelid, and 5 cases from the cheek. The patients were aged between 41 and 86 years, with a mean age of 69.26 ± 173.903 years. The mean BCC size was 1.34 ± 3.853 cm, with a range of 0.3 cm to 12.0 cm. The mean tumor invasion depth from the basement epidermal membrane was 0.17 ± 0.035 cm, with a range of 0.03 cm to 1.10 cm. A mean of 5.66 ± 20.938 intraoperative frozen section slides were examined. VEGF was not expressed in 14 of the 35 patients (40.0%), whereas 42.9% of the patients had low expression and 17.1% of the patients had high expression. VEGF expression was significantly associated with age (P = 0.022), size (P = 0.030), site (P = 0.013), tumor invasion depth (P = 0.019), and number of intraoperatively frozen sections (P = 0.003).

These results suggest that VEGF expression as assessed by immunohistochemistry can predict aggressive or poor prognosis in BCC.