Physical Sciences and Mathematics Commons^™

Probing The Link Between Pancratistatin And Mitochondrial Apoptosis Through Changes In The Membrane Dynamics On The Nanoscale, Stuart R. Castillo, Brett W. Rickeard, Mitchell Dipasquale, Michael H.L. Nguyen, Aislyn Lewis-Laurent, Milka Doktorova, Batuhan Kav, Markus S. Miettinen, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt

Chemistry and Biochemistry Publications

Pancratistatin (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 …