title: Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells.
abstract: OBJECTIVE
  Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines.
  
  
  METHODS
  The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting.
  
  
  RESULTS
  Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines.
  
  
  CONCLUSIONS
  Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation.
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Current address: Houston Methodist Gynecologic Oncology AssociatesHouston, TX. USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kilgore
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill Chapel Hill, NC. USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Jackson
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill Chapel Hill, NC. USA.
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Clark
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan UniversityJinan, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan UniversityJinan, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill Chapel Hill, NC. USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jones
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill Chapel Hill, NC. USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Gilliam
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillChapel Hill, NC. USA.
authors.forename: Paola A
authors.initials: PA
authors.lastname: Gehrig
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillChapel Hill, NC. USA.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillChapel Hill, NC. USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
keywords: Endometrial cancer; buformin; invasion; proliferation