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2012 | 17 | 4 |
Tytuł artykułu

Sulphamoylated estradiol analogue induces antiproliferative activity and apoptosis in breast cell lines

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Research into potential anticancer agents has shown that 2-methoxyestradiol exerts antiproliferative activity in vitro and in vivo in an estrogen receptor-independent manner. Due to its limited biological accessibility and rapid metabolic degradation, several new analogues have been developed in recent years. This study investigated the in vitro effects of a novel in silicodesigned compound (C16) in an estrogen receptor-positive breast adenocarcinoma epithelial cell line (MCF-7), an estrogen receptor-negative breast adenocarcinoma epithelial cell line (MDA-MB-231) and a nontumorigenic breast cell line (MCF-12A). Light microscopy revealed decreased cell density, cells blocked in metaphase and the presence of apoptotic characteristics in all three cell lines after exposure to C16 for 24 h. Polarizationoptical transmitted light differential interference contrast revealed the presence of several rounded cells and decreased cell density. The xCELLigence real-time label-independent approach revealed that C16 exerted antiproliferative activity. Significant inhibition of cell growth was demonstrated after 24 h of exposure to 0.2 μM C16 in all three cell lines. However, the non-tumorigenic MCF-12A cell line recovered extremely well after 48 h when compared to the tumorigenic cell lines. This indicates that C16 acts as an antiproliferative agent, possesses antimitotic activity and induces apoptosis in vitro. These features warrant further investigation.
Wydawca
-
Rocznik
Tom
17
Numer
4
Opis fizyczny
p.549-558,fig.,ref.
Twórcy
autor
  • Department of Physiology, University of Pretoria, Pretoria, South Africa
autor
autor
Bibliografia
  • 1. Thaver, V., Lottering, M.L., van Papendorp, D. and Joubert, A. In vitro effects of 2-methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophageal carcinoma cells. Cell. Biochem. Funct. 27 (2009) 205-210.
  • 2. Visagie, M.H. and Joubert, A.M. In vitro effects of 2-methoxyestradiol-bissulphamate on cell numbers, membrane integrity, morphology and possible induction of apoptosis and autophagy in a non-tumorigenic breast epithelial cell line. Cell. Mol. Biol. Lett. 15 (2010) 564-581.
  • 3. Risinger, A.L., Westbrook, C.D., Encinas, M., Mülbaier, M., Schultes, C.M., Wawro, S., Lewis, J.D., Janssen, B., Giles, F.J. and Moolberry, S.L. ELR5010444, a novel microtubule disruptor with multiple mechanisms of action. Pharmacol. Exp. Ther. 6 (2011) 652-660.
  • 4. Stander, B.A., Marais, S., Vorster, C.J. and Joubert, A.M. In vitro effects of 2-methoxyestradiol on morphology, cell cycle progression, cell death and gene expression changes in the tumorigenic MCF-7 breast epithelial cell line. J. Steroid Biochem. Mol. Biol. 119 (2010) 149-160.
  • 5. Mqoco, T., Marais, S. and Joubert, A. Influence of estradiol analogue on cell growth, morphology and death in oesophageal carcinoma cells. Biocell 34 (2010) 113-120.
  • 6. Vorster, C.J. and Joubert, A.M. In vitro effects of 2-methoxyestradiol-bissulphamate on cell numbers, morphology and cell cycle dynamics in the MCF-7 breast adenocarcinoma cell line. Biocell 34 (2010) 71-79.
  • 7. Newman, S.P., Leese, M.P., Purohit, A., James, D.R.C., Rennie, C.E. and Potter, B.V.L. Inhibition of in vitro angiogenesis by 2-Methoxy- and 2- ethyl-estrogen sulfamates. Int. J. Cancer 109 (2004) 533-540.
  • 8. Newman, S.P., Foster, P.A., Ho, Y.T., Day, J.M., Raibaikady, B., Kasprzyk, P.G., Leese, M.P., Potter, B.V., Reed, M.J. and Purohit, A. The therapeutic potential of a series of bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers. Br. J. Cancer 97 (2007) 1673-1682.
  • 9. Visagie, M.H. and Joubert, A.M. 2-Methoxyestradiol-bis-sulfamate induces apoptosis and autophagy in a tumorigenic breast epithelial cell line. Mol. Cell. Biochem. 357 (2011) 343-352.
  • 10. Chua, Y.S., Chua, Y.L. and Hagen, T. Structure activity analysis of 2-methoxyestradiol analogues reveals targeting of microtubules as major mechanism of antiproliferative and proapoptotic activity. Mol. Cancer Ther. 9 (2010) 224-235.
  • 11. LaVallee, T.M., Burke, P.A., Swartz, G.M., Hamel, E., Agoston, G.E., Shah, J., Suwandi, L., Hanson, A.D., Fogler, A.D., Sidor, C.F. and Treston, A.M. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol. Cancer. Ther. 7 (2008) 1472-1482.
  • 12. Moser, C., Lang, S.A., Mori, A., Hellerbrand, C., Schlitt, H.J., Geissler, E.K., Fogler, W.E. and Stoelzing, O. ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma (HCC) cells, and inhibits growth and vascularization in vivo. BMC Cancer 8 (2008) 206-217.
  • 13. Stanway, S.J., Delavault, P., Purohit, A., Woo, L.W., Thurieau, C., Potter, B.V. and Reed, M.J. Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist 12 (2007) 370-374.
  • 14. Purohit, A., Woo, L.W.L., Chander, S.K., Newman, S.P., Ireson, C., Ho, Y., Grasso, A., Leese, M.P., Potter B.V. and Reed, M.J. Steroid sulphatase inhibitors for breast cancer therapy. J. Steroid Biochem. Mol. Biol. 89 (2003) 423-432.
  • 15. Sutherland, T.E., Anderson, R.L., Hughes, R.A., Altmann, E., Schuliga, M., Ziogas, J. and Stewart, A.G. 2-Methoxyestradiol- a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discov. Today 12 (2007) 577-584.
  • 16. Stander, A., Joubert, F. and Joubert, A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogues. Chem. Biol. Drug Des. 77 (2011) 173-181.
  • 17. Stander, X.X., Stander, B.A. and Joubert, A.M. In vitro effects of an in silico-modelled 17β-estradiol deravitive in combination with dichloroacetic acid on MCF-7 and MCF-12A cells. Cell Prolif. 44 (2011) 567-581.
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-cb5d4496-ac73-4501-b23b-058c2927f2d7
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