Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Kosin University College of Medicine
2019-12-01
|
| Series: | Kosin Medical Journal |
| Subjects: | |
| Online Access: | http://www.kosinmedj.org/upload/pdf/ksmc034-02-13.pdf |
| _version_ | 1797989203283279872 |
|---|---|
| author | Cho Eui Jin Jung Hyun Lee Geun Joo Kim Tae Hwa Lee |
| author_facet | Cho Eui Jin Jung Hyun Lee Geun Joo Kim Tae Hwa Lee |
| author_sort | Cho Eui Jin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T08:16:28Z |
| format | Article |
| id | doaj.art-f106bada2c1e48a3ab9bbc443e729c7a |
| institution | Directory Open Access Journal |
| issn | 2005-9531 |
| language | English |
| last_indexed | 2024-04-11T08:16:28Z |
| publishDate | 2019-12-01 |
| publisher | Kosin University College of Medicine |
| record_format | Article |
| series | Kosin Medical Journal |
| spelling | doaj.art-f106bada2c1e48a3ab9bbc443e729c7a2022-12-22T04:35:10ZengKosin University College of MedicineKosin Medical Journal2005-95312019-12-0134210611610.7180/kmj.2019.34.2.10690Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma CellsCho Eui Jin0Jung Hyun Lee1Geun Joo Kim2Tae Hwa Lee3Department of Obstetrics and Gynecology, College of Medicine, Kosin University, Busan, .KoreaDepartment of Pediatrics, College of Medicine, Kosin University, Busan, .KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Kosin University, Busan, .KoreaDepartment of Obstetrics and Gynecology, College of Medicine, Kosin University, Busan, .KoreaObjectives 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.http://www.kosinmedj.org/upload/pdf/ksmc034-02-13.pdfangiogenesisgenipinhypoxiahypoxia-inducible factor-1vegf |
| spellingShingle | Cho Eui Jin Jung Hyun Lee Geun Joo Kim Tae Hwa Lee Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells Kosin Medical Journal angiogenesis genipin hypoxia hypoxia-inducible factor-1 vegf |
| title | Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells |
| title_full | Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells |
| title_fullStr | Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells |
| title_full_unstemmed | Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells |
| title_short | Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells |
| title_sort | genipin inhibits hypoxia induced accumulation of hif 1α and vegf expressions in human cervical carcinoma cells |
| topic | angiogenesis genipin hypoxia hypoxia-inducible factor-1 vegf |
| url | http://www.kosinmedj.org/upload/pdf/ksmc034-02-13.pdf |
| work_keys_str_mv | AT choeuijin genipininhibitshypoxiainducedaccumulationofhif1aandvegfexpressionsinhumancervicalcarcinomacells AT junghyunlee genipininhibitshypoxiainducedaccumulationofhif1aandvegfexpressionsinhumancervicalcarcinomacells AT geunjookim genipininhibitshypoxiainducedaccumulationofhif1aandvegfexpressionsinhumancervicalcarcinomacells AT taehwalee genipininhibitshypoxiainducedaccumulationofhif1aandvegfexpressionsinhumancervicalcarcinomacells |