Gutenberg Open Science

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ZeitschriftenaufsatzAccess status: Open Access ,
A sphingosine kinase inhibitor combined with temozolomide induces glioblastoma cell death through accumulation of dihydrosphingosine and dihydroceramide, endoplasmic reticulum stress and autophagy
(2014) Noack, J.; Choi, J.; Richter, K.; Kopp-Schneider, A.; Régnier-Vigouroux, Anne
Glioblastomas (GBMs) are very aggressive tumors with low chemosensitivity. The DNA-alkylating agent temozolomide (TMZ) is currently the most efficient chemotoxic drug for GBM therapy; however, many patients develop resistance to TMZ. Combining TMZ with another agent could present an improved treatment option if it could overcome TMZ resistance and avoid side effects. Sphingosine kinase inhibitors (SKIs) have emerged as anticancer agents. Sphingosine kinases are often overexpressed in tumors where their activity of phosphorylating sphingosine (Sph) contributes to tumor growth and migration. They control the levels of the pro-apoptotic ceramide (Cer) and Sph and of the pro-survival sphingosine-1 phosphate. In the present work, TMZ was combined with a specific SKI, and the cytotoxic effect of each drug alone or in combination was tested on GBM cell lines. The combination of sublethal doses of both agents resulted in the cell death potentiation of GBM cell lines without affecting astrocyte viability. It triggered a caspase-3-dependent cell death that was preceded by accumulation of dihydrosphingosine (dhSph) and dihydroceramide (dhCer), oxidative stress, endoplasmic reticulum stress, and autophagy. Autophagy was identified as the crucial switch that facilitated induction of this cell death potentiation. The sublethal dose of the inhibitor induced these stress events, whereas that of TMZ induced the destructive autophagy switch. Remarkably, neither Cer nor Sph, but rather the Cer intermediates, dhSph and dhCer, was involved in the cytotoxicity from the combination. Cell lines sensitive to the combination expressed low levels of the antioxidant enzyme glutathione peroxidase-1, indicating this enzyme as a potential marker of sensitivity to such treatment. This work shows for the first time a strong interaction between a SKI and TMZ, leading to a tumor cell-specific death induction. It further demonstrates the biological relevance of dihydrosphingolipids in cell death mechanisms and emphasizes the potential of drugs that affect sphingolipid metabolism for cancer therapy.
ZeitschriftenaufsatzAccess status: Open Access ,
Energy-efficient field-free switching by orbital torque and spin-reorientation
(2026) Jamshed, Bilal; Das, Subhakanta; Mishra, Pinkesh Kumar; Mah, Wai Lum William; Kläui, Mathias; Piramanayagam, S. N.
Spin-orbit torque has emerged as a leading strategy for low-power magnetisation switching in modern spintronics. To date, most efforts have focused on boosting spin currents via the spin Hall effect, exploiting only the electron's spin while largely ignoring its orbital angular momentum. Meanwhile, deterministic switching of perpendicular magnetic anisotropy layers typically requires an external in-plane field to break inversion symmetry, adding power overhead and hindering large-scale deployment. Here, we demonstrate energy-efficient field-free magnetisation switching enabled by spin reorientation in a synthetic antiferromagnetic structure and enhanced by orbital torque. By tuning the exchange coupling field and magnetic anisotropy of the synthetic antiferromagnetic samples, we achieved a magnetisation switching of 96% utilising both spin and orbital torque. Furthermore, increasing the orbital Hall layer thickness by 15 nm leads to an 85% enhancement of damping-like torque efficiency compared to the reference sample with a Pt layer as the spin source. These results demonstrate orbital angular momentum transport as an efficient torque-generation mechanism in synthetic antiferromagnetic heterostructures, offering a scalable route toward low-power spintronic devices.
ZeitschriftenaufsatzAccess status: Open Access ,
Time-resolved magnetic force microscopy of all-optical magnetization switching
(2026) Khusyainov, Dinar; Liefferink, Rein; Kammerbauer, Fabian; Frömter, Robert; Kläui, Mathias; Kozodaev, Dmitry; Mentink, Johan H.; Afanasiev, Dmytro; Rasing, Theo; Kimel, Alexey
Understanding spin dynamics at ever shorter time and smaller length scales is one of the major challenges in fundamental and applied magnetism, leading in particular to the discovery of giant magnetoresistance and All-Optical Switching (AOS) of magnetization and motivating the development of large-scale facilities such as x-ray free-electron lasers. Here, we propose a conceptually distinct approach to explore ultrafast laser-induced spin dynamics at the nanoscale by combining tabletop Magnetic Force Microscopy (MFM) with femtosecond laser excitation. By writing magnetic domains not with a single but with a pair of mutually delayed ultrashort laser pulses, we observe the spin dynamics by analyzing the final static nanotextured domain pattern as a function of pump-to-pump delay. We show that using MFM, we are able to deduce not only the average reversed magnetization but also the switched areas of nanoscale domains with picosecond temporal resolution. The capabilities of the technique are further demonstrated by applying it to study ultrafast helicity-dependent AOS of magnetization in ferromagnetic Pt/Co/Pt, where magnetization can be reversed with a pair of 100-fs and 3-ps laser pulses. Tracking the laser-induced area of the nanotextured domains as a function of the time separation between the pump pulses reveals critical slowing down of the spin dynamics near the Curie temperature of Co, thereby increasing the efficiency of dual-pulse AOS.