Cytotoxicity of the novel anti-cancer drug rViscumin depends on HER-2 levels in SKOV-3 cells

Biochemical and Biophysical Research Communications
Shaker AbuharbeidAchim Aigner

Abstract

rViscumin is a recombinant mistletoe lectin under clinical investigation as new anti-cancer drug. The relationship between oncogene, e.g., HER-2/neu (c-erbB2) receptor activation and tumor cell chemosensitivity, is of considerable importance to better predict the response to chemotherapy. Here, we analyze the cellular and molecular effects of HER-2 expression on rViscumin chemotoxicity in SKOV-3 cells. We show that selective depletion of HER-2 by ribozyme-targeting markedly decreases cellular sensitivity towards rViscumin. These findings are confirmed by treatment with the well-established inhibitory HER-2 antibody trastuzumab (Herceptin). Using clonal ribozyme-transfected cell lines, we establish a 'HER-2 gene dose' dependence of rViscumin cytotoxicity, which is due to differential induction of apoptosis and is not mediated by cell cycle alterations or altered cellular rViscumin binding/internalization. We further demonstrate an rViscumin-mediated, HER-2-dependent down-regulation of bcl-2 and the dose-dependent activation of members of the MAPK family, p42/44, SAPK/JNK, and p38, but not of caspases-3 and -7.

References

Jan 1, 1992·Cytometry·Z DarzynkiewiczF Traganos
Nov 24, 1995·Science·Z XiaM E Greenberg
Oct 1, 1993·Human Pathology·Y YamanakaM Korc
Apr 28, 1997·Toxicology Letters·J M WilliamsC M Taylor
Sep 22, 1999·European Journal of Biochemistry·J EckH Lentzen
Oct 3, 1999·European Journal of Biochemistry·J EckH Lentzen
Nov 2, 1999·Biochemical and Biophysical Research Communications·M LangerH Lentzen
May 8, 2000·International Journal of Cancer. Journal International Du Cancer·S S HsiehF Czubayko
Aug 26, 2000·The Journal of Biological Chemistry·D L PersonsJ C Pelling
Dec 1, 1994·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·J Kleijnen, P Knipschild

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Citations

Mar 5, 2016·Frontiers in Plant Science·Nasser SewelamPeer M Schenk
Feb 23, 2008·Biochimica Et Biophysica Acta·Jacqueline M LafkyNita J Maihle
Aug 23, 2005·Biochemical and Biophysical Research Communications·Daniela PintoRui Medeiros
Apr 13, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Heinz ZwierzinaHans Lentzen
Jun 13, 2009·Journal of Experimental & Clinical Cancer Research : CR·Gunver S KienleHelmut Kiene
Jun 30, 2005·International Journal of Cancer. Journal International Du Cancer·Marius GrzelinskiAchim Aigner
Mar 16, 2012·Future Medicinal Chemistry·Jason A WilkenNita J Maihle
Mar 8, 2006·World Journal of Gastroenterology : WJG·Guo-Xian GuanXiang-Fu Zhang
Sep 18, 2020·Protein and Peptide Letters·Loganayaki PeriyasamySridhar Muthusami
Mar 30, 2010·Journal of Ovarian Research·Jason A WilkenNita J Maihle

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