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. 2012 Aug 29;17(4):549–558. doi: 10.2478/s11658-012-0030-7

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

Michelle Visagie 1, Thandi Mqoco 1, Anna Joubert 1,✉
PMCID: PMC6276056  PMID: 22933044

Abstract

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.

Key words: C16, Cancer, Proliferation, MCF-7, MCF-12A, MDA-MB-231, Metaphase, Apoptosis, Xcelligence, Tumorigenic

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Abbreviations used

2ME

2-methoxyestradiol

C16

compound 16

References

  • 1.Thaver V., Lottering M.L., van Papendorp D., 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. 2009;27:205–210. doi: 10.1002/cbf.1557. [DOI] [PubMed] [Google Scholar]
  • 2.Visagie M.H., 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. 2010;15:564–581. doi: 10.2478/s11658-010-0030-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Risinger A.L., Westbrook C.D., Encinas M., Mülbaier M., Schultes C.M., Wawro S., Lewis J.D., Janssen B., Giles F.J., Moolberry S.L. ELR5010444, a novel microtubule disruptor with multiple mechanisms of action. Pharmacol. Exp. Ther. 2011;6:652–660. doi: 10.1124/jpet.110.175331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Stander B.A., Marais S., Vorster C.J., 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. 2010;119:149–160. doi: 10.1016/j.jsbmb.2010.02.019. [DOI] [PubMed] [Google Scholar]
  • 5.Mqoco T., Marais S., Joubert A. Influence of estradiol analogue on cell growth, morphology and death in oesophageal carcinoma cells. Biocell. 2010;34:113–120. [PubMed] [Google Scholar]
  • 6.Vorster C.J., 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. 2010;34:71–79. [PubMed] [Google Scholar]
  • 7.Newman S.P., Leese M.P., Purohit A., James D.R.C., Rennie C.E., Potter B.V.L. Inhibition of in vitro angiogenesis by 2-Methoxy- and 2-ethyl-estrogen sulfamates. Int. J. Cancer. 2004;109:533–540. doi: 10.1002/ijc.20045. [DOI] [PubMed] [Google Scholar]
  • 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., 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. 2007;97:1673–1682. doi: 10.1038/sj.bjc.6604100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Visagie M.H., Joubert A.M. 2-Methoxyestradiol-bis-sulfamate induces apoptosis and autophagy in a tumorigenic breast epithelial cell line. Mol. Cell. Biochem. 2011;357:343–352. doi: 10.1007/s11010-011-0905-3. [DOI] [PubMed] [Google Scholar]
  • 10.Chua Y.S., Chua Y.L., Hagen T. Structure activity analysis of 2-methoxyestradiol analogues reveals targeting of microtubules as major mechanism of antiproliferative and proapoptotic activity. Mol. Cancer Ther. 2010;9:224–235. doi: 10.1158/1535-7163.MCT-09-1003. [DOI] [PubMed] [Google Scholar]
  • 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., Treston A.M. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol. Cancer. Ther. 2008;7:1472–1482. doi: 10.1158/1535-7163.MCT-08-0107. [DOI] [PubMed] [Google Scholar]
  • 12.Moser C., Lang S.A., Mori A., Hellerbrand C., Schlitt H.J., Geissler E.K., Fogler W.E., 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. 2008;8:206–217. doi: 10.1186/1471-2407-8-206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Stanway S.J., Delavault P., Purohit A., Woo L.W., Thurieau C., Potter B.V., Reed M.J. Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist. 2007;12:370–374. doi: 10.1634/theoncologist.12-4-370. [DOI] [PubMed] [Google Scholar]
  • 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., Reed M.J. Steroid sulphatase inhibitors for breast cancer therapy. J. Steroid Biochem. Mol. Biol. 2003;89:423–432. doi: 10.1016/s0960-0760(03)00353-4. [DOI] [PubMed] [Google Scholar]
  • 15.Sutherland T.E., Anderson R.L., Hughes R.A., Altmann E., Schuliga M., Ziogas J., Stewart A.G. 2-Methoxyestradiol-a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discov. Today. 2007;12:577–584. doi: 10.1016/j.drudis.2007.05.005. [DOI] [PubMed] [Google Scholar]
  • 16.Stander A., Joubert F., Joubert A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogues. Chem. Biol. Drug Des. 2011;77:173–181. doi: 10.1111/j.1747-0285.2010.01064.x. [DOI] [PubMed] [Google Scholar]
  • 17.Stander X.X., Stander B.A., 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. 2011;44:567–581. doi: 10.1111/j.1365-2184.2011.00789.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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