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Geun Joo Kim 1 Article
Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells
Cho Eui Jin, Jung Hyun Lee, Geun Joo Kim, Tae Hwa Lee
Kosin Med J. 2019;34(2):106-116.   Published online December 31, 2019
DOI: https://doi.org/10.7180/kmj.2019.34.2.106
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Abstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
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.

Citations

Citations to this article as recorded by  
  • Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases
    Magdalena Bryś, Karina Urbańska, Beata Olas
    International Journal of Molecular Sciences.2022; 23(2): 902.     CrossRef
  • The Effects of Natural and Synthetic Blue Dyes on Human Health: A Review of Current Knowledge and Therapeutic Perspectives
    Beata Olas, Jacek Białecki, Karina Urbańska, Magdalena Bryś
    Advances in Nutrition.2021; 12(6): 2301.     CrossRef
  • Polyphenols Extracted from Chinese Hickory (Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells
    Zhiping He, Shaozhen Wu, Ju Lin, Ashley Booth, Gary O’Neal Rankin, Ivan Martinez, Yi Charlie Chen
    Applied Sciences.2020; 10(23): 8615.     CrossRef

KMJ : Kosin Medical Journal