HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Induction of apoptosis in endometrial cancer cells by psammaplysene A involves FOXO1.

AbstractOBJECTIVE:
Endometrial cancer is the most common type of gynecologic cancer in the United States. In this study, we propose that a marine sponge compound, psammaplysene A (PsA) induces apoptosis in endometrial cancer cells through forced nuclear expression of FOXO1.
METHODS:
Ishikawa and ECC1 cells were treated with varying doses of PsA. FOXO1 protein localization was observed using immunofluorescent staining of cells. The effects of PsA on cell viability and proliferation were assessed using a cell viability assay and a BrdU incorporation assay respectively. Cell cycle analysis was performed using flow cytometry. To assess the role of FOXO1 in PsA-induced apoptosis, FOXO1 was silenced in ECC1 cells using siRNA technique, and overexpressed in Ishikawa cells using an adenovirus containing FOXO1 cDNAs. Western blots were used to measure levels of FOXO1 and cleaved PARP proteins.
RESULTS:
Treatment of both ECC1 and Ishikawa cells with PsA caused an increase in nuclear FOXO1 protein, a dramatic decrease in cell viability of approximately 5-fold (p<0.05) and minimal effect on proliferation. Furthermore, treatment of cells with PsA doubled the percentage of cells in the G2/M phase (p<0.05). PsA induced apoptosis in endometrial cancer cells. When FOXO1 was silenced in ECC1 cells and treated with PsA, the incidence of apoptosis decreased. In addition, overexpression of FOXO1 with PsA treatment increased apoptosis.
CONCLUSIONS:
Increasing nuclear FOXO1 function is important for the induction of apoptosis of endometrial cancer cells by PsA.
AuthorsEmily Berry, Jennifer L Hardt, Jon Clardy, John R Lurain, J Julie Kim
JournalGynecologic oncology (Gynecol Oncol) Vol. 112 Issue 2 Pg. 331-6 (Feb 2009) ISSN: 1095-6859 [Electronic] United States
PMID19041124 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • RNA, Small Interfering
  • psammaplysene A
  • Tyrosine
Topics
  • Apoptosis (drug effects)
  • Cell Division (drug effects)
  • Cell Growth Processes (drug effects)
  • Cell Line, Tumor
  • Cell Nucleus (metabolism)
  • Endometrial Neoplasms (drug therapy, genetics, metabolism, pathology)
  • Female
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors (biosynthesis, genetics, metabolism)
  • G2 Phase (drug effects)
  • Humans
  • RNA, Small Interfering (genetics)
  • Transfection
  • Tyrosine (analogs & derivatives, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: