Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells.

International Journal of Molecular Sciences
Lamya H Al-WahaibiGamal A Shazly

Abstract

Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV-TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors-FLV concentration, TAT concentration, and pH of the medium-while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV-TAT preparation. In conclus...Continue Reading

References

Feb 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N B Javitt
Oct 28, 1998·Experimental Gerontology·R Sgonc, J Gruber
Apr 14, 1999·Cell Death and Differentiation·A G Porter, R U Jänicke
Aug 30, 2000·Human & Experimental Toxicology·N S AstonG S Evans
Mar 23, 2001·Anti-cancer Drugs·M MazelJ Temsamani
Nov 2, 2002·The Journal of Biological Chemistry·Jean Philippe RichardBernard Lebleu
Nov 6, 2002·Clinica Chimica Acta; International Journal of Clinical Chemistry·Frederick L Kiechle, Xinbo Zhang
Jun 24, 2005·Journal of Zhejiang University. Science. B·Lin ZhengMaria S Salvato
Dec 13, 2005·Nature Reviews. Cancer·Marie-France DemierreScott M Lippman
Jul 27, 2006·Expert Opinion on Drug Metabolism & Toxicology·José V CastellMaría José Gómez-Lechón
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·Danielle R L Browning, Richard M Martin
Jun 9, 2007·American Journal of Respiratory Cell and Molecular Biology·Christopher M CarlinDavid J Welsh
Dec 22, 2007·Expert Opinion on Drug Delivery·Camilla Foged, Hanne Moerck Nielsen
Jun 19, 2008·Apoptosis : an International Journal on Programmed Cell Death·Hiroo NakajimaTakehiko Koji
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alicja DabrowskaAnna Aldovini
Dec 27, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H H J GeretsF A Atienzar
Oct 9, 2009·The Journal of General Virology·Bizhan RomaniRichard H Glashoff
Oct 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shi-Meng ZhangPing-Kun Zhou
Sep 15, 2010·Gynecologic Oncology·Barbie Taylor-HardingAndrew J Li
Sep 18, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Oskar GonzalezRosa Maria Jiménez
Oct 16, 2010·Seminars in Cancer Biology·Ju Dong YangLewis R Roberts
Oct 30, 2010·Molecular Membrane Biology·Pinaki DesaiMandip Singh
Dec 19, 2013·International Journal of Cancer. Journal International Du Cancer·S IshikawaH Baba
Jun 7, 2014·Pharmacological Reports : PR·Adrianna Sławińska-BrychMartyna Kandefer-Szerszeń
Aug 13, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Siegmund Reissmann
Feb 6, 2015·Bioconjugate Chemistry·Hassan TraboulsiÉric Marsault
Feb 28, 2015·Journal of the National Cancer Institute·Katherine A McGlynnVikrant V Sahasrabuddhe
Jul 24, 2015·Methods in Molecular Biology·Edmond DupontAlain Joliot
Oct 1, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Osman SalisNermin Kılıç
Feb 4, 2016·International Journal of Molecular Sciences·Mie KristensenHanne Mørck Nielsen
Feb 19, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tracey G SimonAdeel A Butt
Feb 24, 2016·Artificial Cells, Nanomedicine, and Biotechnology·Ali F A AlzubaidiOsama A A Ahmed
Apr 26, 2016·International Journal of Nanomedicine·Ahmed S ZidanBader M Aljaeid

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Citations

Nov 22, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Basma G EidFilippo Caraci

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Methods Mentioned

BETA
Flow Cytometry
ELISA

Software Mentioned

Minitab Statistical
SPSS
Minitab
CELLQUEST

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