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000917482 0247_ $$2doi$$a10.1021/acs.molpharmaceut.1c00926
000917482 0247_ $$2ISSN$$a1543-8384
000917482 0247_ $$2ISSN$$a1543-8392
000917482 0247_ $$2pmid$$a35559658
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000917482 037__ $$aFZJ-2023-00695
000917482 082__ $$a610
000917482 1001_ $$0P:(DE-HGF)0$$aCastillo, Stuart R.$$b0
000917482 245__ $$aProbing the Link between Pancratistatin and Mitochondrial Apoptosis through Changes in the Membrane Dynamics on the Nanoscale
000917482 260__ $$aWashington, DC$$bAmerican Chemical Society$$c2022
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000917482 520__ $$aPancratistatin (PST) is a natural antiviral alkaloid that has demonstrated specificity toward cancerous cells and explicitly targets the mitochondria. PST initiates apoptosis while leaving healthy, noncancerous cells unscathed. However, the manner by which PST induces apoptosis remains elusive and impedes the advancement of PST as a natural anticancer therapeutic agent. Herein, we use neutron spin-echo (NSE) spectroscopy, molecular dynamics (MD) simulations, and supporting small angle scattering techniques to study PST's effect on membrane dynamics using biologically representative model membranes. Our data suggests that PST stiffens the inner mitochondrial membrane (IMM) by being preferentially associated with cardiolipin, which would lead to the relocation and release of cytochrome c. Second, PST has an ordering effect on the lipids and disrupts their distribution within the IMM, which would interfere with the maintenance and functionality of the active forms of proteins in the electron transport chain. These previously unreported findings implicate PST's effect on mitochondrial apoptosis.
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000917482 7001_ $$0P:(DE-HGF)0$$aRickeard, Brett W.$$b1
000917482 7001_ $$0P:(DE-HGF)0$$aDiPasquale, Mitchell$$b2
000917482 7001_ $$0P:(DE-HGF)0$$aNguyen, Michael H. L.$$b3
000917482 7001_ $$0P:(DE-HGF)0$$aLewis-Laurent, Aislyn$$b4
000917482 7001_ $$0P:(DE-HGF)0$$aDoktorova, Milka$$b5
000917482 7001_ $$0P:(DE-Juel1)178946$$aKav, Batuhan$$b6
000917482 7001_ $$00000-0002-3999-4722$$aMiettinen, Markus S.$$b7
000917482 7001_ $$00000-0003-3617-251X$$aNagao, Michihiro$$b8
000917482 7001_ $$00000-0002-6128-8517$$aKelley, Elizabeth G.$$b9
000917482 7001_ $$00000-0001-6848-2497$$aMarquardt, Drew$$b10$$eCorresponding author
000917482 773__ $$0PERI:(DE-600)2132489-X$$a10.1021/acs.molpharmaceut.1c00926$$gVol. 19, no. 6, p. 1839 - 1852$$n6$$p1839 - 1852$$tMolecular pharmaceutics$$v19$$x1543-8384$$y2022
000917482 8564_ $$uhttps://juser.fz-juelich.de/record/917482/files/acs.molpharmaceut.1c00926.pdf
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000917482 9141_ $$y2022
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