Statins inhibit tumor progression via an enhancer of zeste homolog 2-mediated epigenetic alteration in colorectal cancer

International Journal of Cancer. Journal International Du Cancer
S IshikawaHideo Baba

Abstract

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin-mediated antiproliferative effects depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27(KIP1) expression in the resected CRC by immunohistochemical staining and resulted in th...Continue Reading

References

Feb 1, 1990·Nature·J L Goldstein, M S Brown
Oct 25, 1996·The Journal of Biological Chemistry·R SatoM Maeda
Dec 18, 1998·American Journal of Clinical Oncology·J LarnerM Shaffrey
Oct 11, 2002·Nature·Sooryanarayana VaramballyArul M Chinnaiyan
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
May 27, 2005·The New England Journal of Medicine·Jenny N PoynterGad Rennert
Jul 21, 2005·International Journal of Radiation Oncology, Biology, Physics·Matthew S KatzJose G Guillem
Aug 30, 2008·Mutation Research·Jeffrey A Simon, Carol A Lange
Sep 24, 2009·British Journal of Cancer·Ø FlugeUNKNOWN Norwegian Gastrointestinal Cancer Group
Aug 19, 2011·Journal of the National Cancer Institute·Kimmie NgCharles S Fuchs

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Citations

Aug 25, 2015·Journal of Microencapsulation·Emilia LicareteManuela Banciu
Feb 2, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·P C OrsolinJ C Nepomuceno
Sep 30, 2015·Annals of Surgical Oncology·Ryuma TokunagaHideo Baba
May 17, 2015·Cancer Genetics·Heidrun KarlicFranz Varga
Jan 22, 2015·Oncology Reports·Abdullah K Altwairgi
Sep 16, 2017·International Journal of Molecular Sciences·Heidrun KarlicFranz Varga
Apr 21, 2018·Future Medicinal Chemistry·Zdeněk KejíkVladimír Král
Dec 13, 2018·Current Drug Targets·Meysam GachpazanAmir Avan
Jun 4, 2017·The Journal of Pharmacology and Experimental Therapeutics·Stephanie C Allen, Cyril D S Mamotte
Aug 28, 2020·European Journal of Clinical Investigation·Nooshin MohammadzadehAmirhossein Sahebkar
Dec 14, 2018·Cardiology and Therapy·Keshav Kumar GuptaRanjodh Singh Sanghera
Aug 20, 2019·Molecular and Clinical Oncology·Brian P RutledgeMichael S Simon
Jun 14, 2020·International Journal of Molecular Sciences·Lamya H Al-WahaibiGamal A Shazly
Jun 15, 2016·International Journal of Cancer. Journal International Du Cancer·Xin ZhangChuanxin Wang
Sep 8, 2016·Cold Spring Harbor Perspectives in Medicine·Yixuan Li, Edward Seto
Oct 25, 2017·Scientific Reports·Laura Vilorio-MarquésAntonio J Molina
Jan 3, 2021·Ecotoxicology and Environmental Safety·Nélson AlvesMiguel M Santos
May 11, 2020·Life Sciences·Armita Mahdavi GorabiAmirhossein Sahebkar
Jul 27, 2021·Frontiers in Immunology·Esha SehanobishElina Jerschow
Oct 18, 2021·Veterinary and Comparative Oncology·Takuro IshikawaKatsuhiko Warita

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Methods Mentioned

BETA
PCR
transfection

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SPSS

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