Literature DB >> 30018708

Topiramate exhibits anti-tumorigenic and metastatic effects in ovarian cancer cells.

Guangxu Xu1,2, Ziwei Fang2,3, Leslie H Clark2,4, Wenchuan Sun2, Yajie Yin2, Rong Zhang1, Stephanie A Sullivan2, Arthur-Quan Tran2, Weimin Kong5, Jiandong Wang5, Chunxiao Zhou2,4, Victoria L Bae-Jump2,4.   

Abstract

Ovarian cancer is one of the leading causes of cancer related deaths among women worldwide, with an overall 5-year survival of only 30-40%. Carbonic anhydrases are up-regulated in many types of cancer and play an important role in tumor progression and metastasis. Carbonic anhydrase 9 has been implicated as a potential anti-tumorigenic target. Topiramate (TPM) is a potent inhibitor of carbonic anhydrase isozymes, including carbonic anhydrase 9, and has been shown to have anti-tumorigenic activity in several cancer types. Our goal was to evaluate the effect of TPM on cell proliferation and to identify possible mechanisms by which TPM inhibits cell growth in ovarian cancer. TPM significantly inhibited ovarian cancer cell proliferation and induced cell cycle G1 arrest, cellular stress and apoptosis through the AKT/mTOR and MAPK pathways. TPM also exerted anti-metastatic effects by decreasing the adhesion and invasion of ovarian cancer cells and affecting the expression of critical regulators of the epithelial-mesenchymal transition (EMT). Our findings demonstrate that TPM has anti-tumorigenic effects in ovarian cancer and is worthy of further exploration in clinical trials.

Entities:  

Keywords:  Ovarian cancer; carbonic anhydrases; invasion; topiramate

Year:  2018        PMID: 30018708      PMCID: PMC6038080     

Source DB:  PubMed          Journal:  Am J Transl Res            Impact factor:   4.060


  56 in total

Review 1.  Objective response rate is a possible surrogate endpoint for survival in patients with advanced, recurrent ovarian cancer.

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Journal:  Gynecol Oncol       Date:  2017-04-08       Impact factor: 5.482

2.  Carbonic anhydrase IX promotes tumor growth and necrosis in vivo and inhibition enhances anti-VEGF therapy.

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Journal:  Clin Cancer Res       Date:  2012-04-12       Impact factor: 12.531

3.  Expression of transmembrane carbonic anhydrases IX and XII in ovarian tumours.

Authors:  P Hynninen; L Vaskivuo; J Saarnio; H Haapasalo; J Kivelä; S Pastoreková; J Pastorek; A Waheed; W S Sly; U Puistola; S Parkkila
Journal:  Histopathology       Date:  2006-12       Impact factor: 5.087

4.  Activation of HIF-1alpha in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway.

Authors:  Frédéric Dayan; Rebecca L Bilton; Julie Laferrière; Eric Trottier; Danièle Roux; Jacques Pouyssegur; Nathalie M Mazure
Journal:  J Cell Physiol       Date:  2009-01       Impact factor: 6.384

5.  Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with beta-catenin.

Authors:  Eliska Svastová; Norbert Zilka; Miriam Zat'ovicová; Adriana Gibadulinová; Fedor Ciampor; Jaromír Pastorek; Silvia Pastoreková
Journal:  Exp Cell Res       Date:  2003-11-01       Impact factor: 3.905

Review 6.  Sulfamates and their therapeutic potential.

Authors:  Jean-Yves Winum; Andrea Scozzafava; Jean-Louis Montero; Claudiu T Supuran
Journal:  Med Res Rev       Date:  2005-03       Impact factor: 12.944

7.  PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines.

Authors:  Norazizah Shafee; Stefan Kaluz; Ning Ru; Eric J Stanbridge
Journal:  Cancer Lett       Date:  2009-04-01       Impact factor: 8.679

Review 8.  Carbonic anhydrase IX as an imaging and therapeutic target for tumors and metastases.

Authors:  Narges K Tafreshi; Mark C Lloyd; Marilyn M Bui; Robert J Gillies; David L Morse
Journal:  Subcell Biochem       Date:  2014

9.  Identifying the stromal cell type that contributes to tumor aggressiveness associated with carbonic anhydrase IX.

Authors:  Pinaki Bose; Joseph C Dort; Nigel T Brockton
Journal:  Cell Cycle       Date:  2013-07-30       Impact factor: 4.534

10.  Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers.

Authors:  Kyungbin Kim; Won Young Park; Jee Yeon Kim; Mee Young Sol; Dong Hun Shin; Do Youn Park; Chang Hun Lee; Jeong Hee Lee; Kyung Un Choi
Journal:  Korean J Pathol       Date:  2012-12-26
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  4 in total

Review 1.  Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.

Authors:  Alina L Capatina; Dimitris Lagos; William J Brackenbury
Journal:  Rev Physiol Biochem Pharmacol       Date:  2022       Impact factor: 5.545

Review 2.  Synergy Between Low Dose Metronomic Chemotherapy and the pH-centered Approach Against Cancer.

Authors:  Tomas Koltai; Rosa A Cardone; Stephan J Reshkin
Journal:  Int J Mol Sci       Date:  2019-10-31       Impact factor: 5.923

Review 3.  Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment.

Authors:  Concetta Altamura; Maria Raffaella Greco; Maria Rosaria Carratù; Rosa Angela Cardone; Jean-François Desaphy
Journal:  Cancers (Basel)       Date:  2021-02-07       Impact factor: 6.639

4.  Targeting the pH Paradigm at the Bedside: A Practical Approach.

Authors:  Tomas Koltai
Journal:  Int J Mol Sci       Date:  2020-12-03       Impact factor: 5.923

  4 in total

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