Medroxyprogestogen enhances apoptosis of SKOV-3 cells via inhibition of the PI3K/Akt signaling pathway

We sought to assess the effect of progestin on the apoptosis of epithelial ovarian cancer cell line SKOV-3 and via regulation of phosphorylation signaling in. Epithelial ovarian cancer cell line SKOV-3 was treated with medroxyprogestogen, phosphatidylinositol 3-kinase inhibitor LY294002 and vehicle control. Akt, phospho-Akt, Bcl-2 and phospho-Bad proteins were examined by immunoblotting assays. Medroxyprogestogen-induced apoptosis was assessed by MTT assays and Annexin V apoptosis assay. We found no significant difference in Akt and Bad expression in both the medroxyprogestogen groups and the control group. The levels of phospho-Akt, Bcl-2 and phospho-Bad were decreased in all the medroxyprogestogen groups and significantly decreased in the high dose mitogen-activated protein (MAP) group (10 µmol/L). Viability of SKOV-3 was reduced and apparent apoptosis of SKOV-3 cells was observed with increased doses of MAP. The findings suggest that medroxyprogestogen can induce SKOV-3 cell apoptosis by inhibiting Akt phosphorylation.

• Publication year

  2012

• Venue

  Journal of Biomedical Research

• Publication date

  2012-12-10

• Fields of study

  Medicine

• Identifiers
  DOI 10.7555/JBR.27.20120051PMID 23554793PMCID 3596754
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The observed apoptosis is consistent with medroxyprogestogen suppressing the PI3K/Akt signaling pathway through reduced Akt phosphorylation.

  Confidence 0.93

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• Medroxyprogestogen lowered phospho-Akt, Bcl-2, and phospho-Bad levels in SKOV-3 cells.

  Confidence 0.96

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• Viability of SKOV-3 cells decreased and apoptosis increased as medroxyprogestogen dose rose.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review

• apoptosis

  process

  Programmed cell death measured as an outcome in the assays.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• bcl-2

  protein

  An anti-apoptotic Bcl-2 family protein measured by immunoblotting.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• medroxyprogestogen

  compound

  A progestin compound administered to SKOV-3 cells in the experiment.

  Aliases: MAP

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• phospho-akt

  protein

  The phosphorylated form of Akt measured by immunoblotting.

  Aliases: Akt phosphorylation

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• phospho-bad

  protein

  The phosphorylated form of Bad measured by immunoblotting.

  Aliases: phosphorylated Bad

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• pi3k/akt signaling pathway

  signaling pathway

  A cell signaling pathway involving PI3K and Akt that was examined in the study.

  Aliases: phosphatidylinositol 3-kinase/Akt signaling pathway

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• skov-3 cell line

  cell line

  A human epithelial ovarian cancer cell line used as the experimental model.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review

• Cancer Statistics, 2009

  2010cited by this paper
• Apoptosis and cancer: the genesis of a research field

  2009cited by this paper
• Prognostic value of estrogen receptor and progesterone receptor status in young Chinese ovarian carcinoma patients.

  2009cited by this paper
• Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway.

  2009cited by this paper
• Expressions of Estrogen and Progesterone Receptors in Epithelial Ovarian Cancer: A Clinicopathologic Study

  2009cited by this paper
• Cancer Statistics, 2009

  2009cited by this paper
• Estrogen and progestin regulate metastasis through the PI3K/AKT pathway in human ovarian cancer.

  2008cited by this paper
• Phosphatidylinositol 3-kinase/Akt regulates the balance between plasminogen activator inhibitor-1 and urokinase to promote migration of SKOV-3 ovarian cancer cells.

  2007cited by this paper
• The Bcl-2 apoptotic switch in cancer development and therapy

  2007cited by this paper
• The FLT3 internal tandem duplication mutation prevents apoptosis in interleukin-3-deprived BaF3 cells due to protein kinase A and ribosomal S6 kinase 1-mediated BAD phosphorylation at serine 112.

  2005cited by this paper
• Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer.

  2004cited by this paper
• Signal transduction targets in invasion

  2004cited by this paper
• Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma.

  2004cited by this paper
• Mammalian target of rapamycin: a new molecular target for breast cancer.

  2003cited by this paper
• Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells.

  2003cited by this paper
• Evaluation of complete surgical staging with pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy for improvement of survival in stage I ovarian clear cell carcinoma.

  2003cited by this paper
• Distinct Role of Phosphatidylinositol 3-Kinase and Rho Family GTPases in Vav3-induced Cell Transformation, Cell Motility, and Morphological Changes*

  2002cited by this paper
• Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis.

  2002cited by this paper
• Survival signaling goes BAD.

  2002cited by this paper
• Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk.

  2002cited by this paper
• The Role of Phosphatidylinositol 3-Kinase, Rho Family GTPases, and STAT3 in Ros-induced Cell Transformation*

  2002cited by this paper
• Differential Requirement for Rho Family GTPases in an Oncogenic Insulin-like Growth Factor-I Receptor-induced Cell Transformation*

  2001cited by this paper
• High-dose progesterone inhibition of urokinase secretion and invasive activity by SKOV-3 ovarian carcinoma cells: evidence for a receptor-independent nongenomic effect on the plasma membrane.

  2001cited by this paper
• Health benefits of oral contraceptives.

  2000cited by this paper
• 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.

  2000cited by this paper
• Differential requirements of the MAP kinase and PI3 kinase signaling pathways in Src- versus insulin and IGF-1 receptors-induced growth and transformation of rat intestinal epithelial cells

  2000cited by this paper
• Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.

  1999cited by this paper
• Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.

  1997cited by this paper
• Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.

  1997cited by this paper
• Endometrial and ovarian cancer and oral contraceptives--findings in a large cohort study.

  1995cited by this paper

• Targeted Therapy of Spinal Cord Injury: Inhibition of Apoptosis Is a Promising Therapeutic Strategy

  2023cites this paper
• The role of PI3K/Akt signalling pathway in spinal cord injury.

  2022cites this paper
• Comparative Transcriptome Analysis of Spleen Reveals Potential Regulation of Genes and Immune Pathways Following Administration of Aeromonas salmonicida subsp. masoucida Vaccine in Atlantic Salmon (Salmo salar)

  2022cites this paper
• Ursolic Acid Decreases the Proliferation of MCF-7 Cell-Derived Breast Cancer Stem-Like Cells by Modulating the ERK and PI3K/AKT Signaling Pathways

  2021cites this paper
• FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice

  2021cites this paper
• Neuroprotective Potential of a Lanosteryl Triterpene from Protorhus longifolia Stem Bark (Benrh.) Engl in high fat diet fed and STZ -induced diabetic neuropathy in rats

  2019cites this paper
• 2,5-Hexanedione mediates neuronal apoptosis through suppression of NGF via PI3K/Akt signaling in the rat sciatic nerve

  2019cites this paper
• 2,5‐hexanedione induces bone marrow mesenchymal stem cell apoptosis via inhibition of Akt/Bad signal pathway

  2018cites this paper
• Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways in vitro

  2017cites this paper
• MicroRNA-34a regulates brain-derived neurotrophic factor in an intracerebral hemorrhage model

  2017cites this paper
• 2,5-hexanedione downregulates nerve growth factor and induces neuron apoptosis in the spinal cord of rats via inhibition of the PI3K/Akt signaling pathway

  2017cites this paper
• Rhus verniciflua Stokes (RVS) and butein induce apoptosis of paclitaxel-resistant SKOV-3/PAX ovarian cancer cells through inhibition of AKT phosphorylation

  2016cites this paper
• Norcantharidin Inhibits Lymphangiogenesis by Downregulating the Expression of VEGF-C and VEGF-D in Human Dermal Lymphatic Endothelial Cells in vitro

  2015cites this paper
• Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-κB/IκBα, and Bcl-2/Bax signaling

  2015cites this paper
• Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway.

  2015cites this paper
• All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression

  2015cites this paper
• Tetrahydrobiopterin reverse left ventricular hypertrophy and diastolic dysfunction through the PI3K/p-Akt pathway in spontaneously hypertensive rats.

  2015cites this paper
• noic acid (ATRA) in congenital clubfoot (CCF)-like deformities in in vivo models, the essential cellular and molecular targets and the signaling mechanisms for ATRA-induced CCF-like deformities remain to be eluci-

  2015cites this paper
• Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF- κ B/i κ B α , and Bcl-2/Bax signaling

  2015cites this paper
• Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF- κ B/i κ B α , and Bcl-2/Bax signaling

  2015cites this paper
• Induced Neural Stem Cells Protect Neuronal Cells against Apoptosis

  2014cites this paper
• Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.

  2014cites this paper
• Enhancement of interaction of BSEP and HAX-1 on the canalicular membrane of hepatocytes in a mouse model of cholesterol cholelithiasis.

  2014cites this paper
• Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K/Akt pathway in rats

  2013cites this paper
• Bis(α-furancarboxylato)oxovanadium(IV) Exerts Durable Antidiabetic Effects and Suppresses Matrix Metalloproteinase-2 Activity in Spontaneous Type 2 Diabetic KKAy Mice

  2013cites this paper