Biochemical disorders induced by cytotoxic marine natural products in breast cancer cells as revealed by proton NMR spectroscopy-based metabolomics

Biochemical Pharmacology
Mathilde Bayet-RobertDaniel Morvan

Abstract

Marine plants and animals are sources of a huge number of pharmacologically active compounds, some of which exhibit antineoplastic activity of clinical relevance. However the mechanism of action of marine natural products (MNPs) is poorly understood. In this study, proton NMR spectroscopy-based metabolomics was applied to unravel biochemical disorders induced in human MCF7 breast cancer cells by 3 lead candidate anticancer MNPs: ascididemin (Asc), lamellarin-D (Lam-D), and kahalalide F (KF). Asc, Lam-D, and KF provoked a severe decrease in DNA content in MCF7 cells after 24-h treatment. Asc and Lam-D provoked apoptosis, whereas KF induced non-apoptotic cell death. Metabolite profiling revealed major biochemical disorders following treatment. The response of MCF7 tumor cells to Asc involved the accumulation of citrate (x17 the control level, P<0.001), testifying enzyme blockade in citrate metabolism, and the accumulation of gluconate (x9.8, P<0.005), a metabolite never reported at such concentration in tumor cells, probably testifying glycolysis shutdown. The response to Lam-D involved the accumulation of aspartate (x7.2, P<0.05), glutamate (x14.7, P<0.05), and lactate (x2.3, P<0.05), probably in relation with the targeting of t...Continue Reading

References

Jul 1, 1995·Brain Research. Molecular Brain Research·V Mehta, M A Namboodiri
Jan 19, 1996·Cancer Letters·M García-RochaJ Avila
Mar 15, 1996·Biochimica Et Biophysica Acta·P MendesH V Westerhoff
Feb 18, 2003·Chemical Research in Toxicology·Sandra S MatsumotoLouis R Barrows
Jul 2, 2004·Nature Reviews. Cancer·Julian L Griffin, John P Shockcor
Mar 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeany M Rademaker-LakhaiJan H M Schellens
Apr 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arvind RamanathanStuart L Schreiber
Jun 15, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J M SewellS M Guichard
Mar 23, 2006·The Journal of Biological Chemistry·Kiyotaka MachidaHiroyuki Osada
Apr 7, 2006·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Daniel MorvanJean Claude Madelmont
Oct 28, 2006·Journal of Natural Products·Sonia ManzanaroJesús Angel de la Fuente
Jan 24, 2007·Physiological Reviews·Jorgina SatrústeguiAraceli Del Arco
Dec 22, 2007·Chemical Reviews·Hui FanJin-Feng Hu
Jan 9, 2008·Apoptosis : an International Journal on Programmed Cell Death·Christoffer TammSandra Ceccatelli
Feb 28, 2008·Journal of Natural Products·Sanjeev BanerjeeRamzi M Mohammad
Jan 28, 2009·Marine Drugs·Dianne BaunbaekLaurent Meijer
Feb 3, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Salvador Martín-AlgarraLuis Paz-Ares
Dec 3, 2009·Molecular Cancer Therapeutics·Caroline BallotPhilippe Marchetti
Feb 13, 2010·Apoptosis : an International Journal on Programmed Cell Death·Caroline BallotPhilippe Marchetti
May 1, 2010·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Mathilde Bayet-RobertDaniel Morvan

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Citations

May 18, 2013·Chemical Reviews·Sandip B BharateRam A Vishwakarma
Feb 24, 2015·Marine Drugs·Christian Bailly
Dec 23, 2014·Marine Drugs·Dennis ImbriTill Opatz
Jun 14, 2016·Journal of Medicinal Chemistry·Michel FrédérichPascal de Tullio
Feb 7, 2020·Expert Opinion on Drug Discovery·Kevin Andrew StuartRuAngelie Edrada-Ebel
May 2, 2017·Briefings in Bioinformatics·Jiansong FangFeixiong Cheng

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis