Literature DB >> 30854075

UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway.

Qiang Wang1, Wei Shi2.   

Abstract

Ovarian cancer is the gynaecological malignancy with the highest mortality rate worldwide, and effective and safe therapeutic methods are limited. UNBS5162, a derivative of naphthalimide, has a clear inhibitory effect on the proliferation of various tumour cells in vitro and in vivo as a pan-antagonist of CXC chemokine ligand expression, but whether it serves a function in ovarian cancer remains unclear. The aim of the present study was to determine the effects of UNBS5162 on the proliferation, migration and invasion of ovarian cancer cells. The cell viability was detected using a Cell Counting Kit-8 (CCK-8) assay. The invasion and migration of SKOV3 cells were determined using Transwell assays. Cell apoptosis was determined using flow cytometry. The apoptosis-associated proteins and associated factors, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway members, were detected using western blot analysis. The CCK-8 assay revealed that SKOV3 cell viability was affected by UNBS5162 in a dose- and time-dependent manner. In Transwell assays, UNBS5162 inhibited cell invasion and migration. Furthermore, it was identified that UNBS5162 markedly increased the apoptosis rate of SKOV3 cells. Simultaneously, the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased and the expression of the pro-apoptotic proteins active caspase-3 and Bcl-2-associated X protein were increased in SKOV3 cells treated with UNBS5162. In addition, the expression levels of phospho (p-)AKT/total AKT, p-mammalian target of rapamycin (mTOR)/total mTOR, p-p70 S6 kinase (p70S6K)/total p70S6K and cyclin D1 were decreased in the UNBS5162-treated group. The results of the present study indicated that UNBS5162 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells, which may be regulated by the PI3K/AKT signalling pathway. These results suggest that UNBS5162 may be a potential novel drug for clinical ovarian cancer treatment.

Entities:  

Keywords:  SKOV3 cell line; UNBS5162; apoptosis; invasion; migration; ovarian cancer; proliferation

Year:  2019        PMID: 30854075      PMCID: PMC6365959          DOI: 10.3892/ol.2019.9890

Source DB:  PubMed          Journal:  Oncol Lett        ISSN: 1792-1074            Impact factor:   2.967


  30 in total

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Authors:  Ippolito Antonini; Rosaria Volpini; Diego Dal Ben; Catia Lambertucci; Gloria Cristalli
Journal:  Bioorg Med Chem       Date:  2008-08-15       Impact factor: 3.641

2.  Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome.

Authors:  Jia Huang; Lin Zhang; Joel Greshock; Theresa A Colligon; Yan Wang; Renee Ward; Dionyssios Katsaros; Heini Lassus; Ralf Butzow; Andrew K Godwin; Joseph R Testa; Katherine L Nathanson; Phyllis A Gimotty; George Coukos; Barbara L Weber; Yan Degenhardt
Journal:  Genes Chromosomes Cancer       Date:  2011-05-11       Impact factor: 5.006

3.  Selenium-containing naphthalimides as anticancer agents: design, synthesis and bioactivity.

Authors:  Liwei Zhao; Jianfeng Li; Yiquan Li; Jianwen Liu; Thomas Wirth; Zhong Li
Journal:  Bioorg Med Chem       Date:  2012-03-01       Impact factor: 3.641

4.  Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma.

Authors:  Daruka Mahadevan; Donald W Northfelt; Pavani Chalasani; Diane Rensvold; Sandra Kurtin; Daniel D Von Hoff; Mitesh J Borad; Raoul Tibes
Journal:  Int J Clin Oncol       Date:  2012-10-11       Impact factor: 3.402

Review 5.  Naphthalimides and azonafides as promising anti-cancer agents.

Authors:  Laurent Ingrassia; Florence Lefranc; Robert Kiss; Tatjana Mijatovic
Journal:  Curr Med Chem       Date:  2009       Impact factor: 4.530

6.  2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity.

Authors:  Eric Van Quaquebeke; Tine Mahieu; Patrick Dumont; Janique Dewelle; Fabrice Ribaucour; Gentiane Simon; Sébastien Sauvage; Jean-François Gaussin; Jérôme Tuti; Mohamed El Yazidi; Frank Van Vynckt; Tatjana Mijatovic; Florence Lefranc; Francis Darro; Robert Kiss
Journal:  J Med Chem       Date:  2007-07-21       Impact factor: 7.446

7.  UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.

Authors:  Tatjana Mijatovic; Tina Mahieu; Céline Bruyère; Nancy De Nève; Janique Dewelle; Gentiane Simon; Mischaël J M Dehoux; Ellen van der Aar; Benjamin Haibe-Kains; Gianluca Bontempi; Christine Decaestecker; Eric Van Quaquebeke; Francis Darro; Robert Kiss
Journal:  Neoplasia       Date:  2008-06       Impact factor: 5.715

8.  Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives.

Authors:  Shenghui Li; Shengjie Xu; Yonghe Tang; Shan Ding; Jinchao Zhang; Shuxiang Wang; Guoqiang Zhou; Chuanqi Zhou; Xiaoliu Li
Journal:  Bioorg Med Chem Lett       Date:  2013-12-14       Impact factor: 2.823

9.  Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.

Authors:  Mette T Faber; Susanne K Kjær; Christian Dehlendorff; Jenny Chang-Claude; Klaus K Andersen; Estrid Høgdall; Penelope M Webb; Susan J Jordan; Mary Anne Rossing; Jennifer A Doherty; Galina Lurie; Pamela J Thompson; Michael E Carney; Marc T Goodman; Roberta B Ness; Francesmary Modugno; Robert P Edwards; Clareann H Bunker; Ellen L Goode; Brooke L Fridley; Robert A Vierkant; Melissa C Larson; Joellen Schildkraut; Daniel W Cramer; Kathryn L Terry; Allison F Vitonis; Elisa V Bandera; Sara H Olson; Melony King; Urmila Chandran; Lambertus A Kiemeney; Leon F A G Massuger; Anne M van Altena; Sita H Vermeulen; Louise Brinton; Nicolas Wentzensen; Jolanta Lissowska; Hannah P Yang; Kirsten B Moysich; Kunle Odunsi; Karin Kasza; Oluwatosin Odunsi-Akanji; Honglin Song; Paul Pharaoh; Mitul Shah; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Rebecca Sutphen; Usha Menon; Simon A Gayther; Susan J Ramus; Aleksandra Gentry-Maharaj; Celeste Leigh Pearce; Anna H Wu; Malcolm C Pike; Harvey A Risch; Allan Jensen
Journal:  Cancer Causes Control       Date:  2013-03-02       Impact factor: 2.506

Review 10.  Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics.

Authors:  Akintunde Akinleye; Parthu Avvaru; Muhammad Furqan; Yongping Song; Delong Liu
Journal:  J Hematol Oncol       Date:  2013-11-22       Impact factor: 17.388

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