Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Zuzana MrkvováIva Slaninová


Tumor suppressor p53 is mutated in about 50% of cancers. Most malignant melanomas carry wild-type p53, but p53 activity is often inhibited due to overexpression of its negative regulators Mdm2 or MdmX. We performed high throughput screening of 2448 compounds on A375 cells carrying p53 activity luciferase reporter construct to reveal compounds that promote p53 activity in melanoma. Albendazole and fenbendazole, two approved and commonly used benzimidazole anthelmintics, stimulated p53 activity and were selected for further studies. The protein levels of p53 and p21 increased upon the treatment with albendazole and fenbendazole, indicating activation of the p53-p21 pathway, while the levels of Mdm2 and MdmX decreased in melanoma and breast cancer cells overexpressing these proteins. We also observed a reduction of cell viability and changes of cellular morphology corresponding to mitotic catastrophe, i.e., G2/M cell cycle arrest of large multinucleated cells with disrupted microtubules. In summary, we established a new tool for testing the impact of small molecule compounds on the activity of p53 and used it to identify the action of benzimidazoles in melanoma cells. The drugs promoted the stability and transcriptional activity o...Continue Reading


Nov 1, 1982·Journal of Medicinal Chemistry·R P GuptaK C Agrawal
Jul 1, 1997·The Veterinary Journal·R J Martin
Aug 31, 2000·Annual Review of Biochemistry·E Nogales
Oct 12, 2000·Nature Cell Biology·Paraskevi GiannakakouTito Fojo
Jan 9, 2001·Clinical Microbiology Reviews·P Upcroft, J A Upcroft
Mar 15, 2001·Cancer Letters·Mohammad H PourgholamiD L Morris
Jul 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Paraskevi GiannakakouTito Fojo
Nov 7, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A SeatonH van den Berg
May 15, 2007·The International Journal of Biochemistry & Cell Biology·Franck Toledo, Geoffrey M Wahl
Aug 1, 2008·Molecular Cancer Research : MCR·Nicole A DoudicanSeth J Orlow
Jun 18, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·I SlaninováJ Slanina
Apr 20, 2010·BMC Cancer·Mohammad H PourgholamiDavid L Morris
Nov 19, 2011·Radiation Oncology·Kirtesh PatelSeth J Orlow
Jul 24, 2012·Nature Medicine·Agnieszka GembarskaJean-Christophe Marine
Sep 18, 2012·Journal of Cancer Science & Therapy·Carlos M Telleria
Jan 11, 2013·Nature Reviews. Cancer·Mark WadeGeoffrey M Wahl
Nov 10, 2013·Current Topics in Medicinal Chemistry·Yong-Tao DuanHai-Liang Zhu
Dec 30, 2014·Current Cancer Drug Targets·Veronika HanušováPetra Matouskova
Jan 6, 2016·The Journal of Pharmacy and Pharmacology·Věra KrálováLenka Skálová
Mar 30, 2016·Annual Review of Pathology·Orit Karni-SchmidtCarol Prives
Oct 7, 2016·Redox Biology·L S E P W CastroR C Pedrosa
Nov 7, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K ČáňováE Rudolf
Jun 21, 2018·ImmunoTargets and Therapy·Beatriz DominguesHelena Pópulo


Oct 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dongdong WangAtanas G Atanasov
Sep 17, 2020·Cell Death & Disease·Monika StetkovaStjepan Uldrijan
Sep 9, 2020·Immune Network·Deok-Soo SonSamuel E Adunyah

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