Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells
10.7180/kmj.2019.34.2.106
- Author:
Cho Eui JIN
1
;
Jung Hyun LEE
;
Geun Joo KIM
;
Tae Hwa LEE
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, Kosin University, Busan, Korea. leehula@hanmail.net
- Publication Type:Original Article
- Keywords:
Angiogenesis;
Genipin;
Hypoxia;
Hypoxia-inducible factor-1;
VEGF
- MeSH:
Anoxia;
Blotting, Western;
Breast Neoplasms;
Cell Line;
Colonic Neoplasms;
Gardenia;
HeLa Cells;
Humans;
Liver Neoplasms;
Luciferases;
Polymerase Chain Reaction;
Prostatic Neoplasms;
Reverse Transcription;
Uterine Cervical Neoplasms;
Vascular Endothelial Growth Factor A
- From:Kosin Medical Journal
2019;34(2):106-116
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
