Deoxynivalenol induces structural alterations in epidermoid carcinoma cells A431 and impairs the response to biomechanical stimulation

脱氧雪腐镰刀菌烯醇诱导表皮样癌细胞 A431 的结构改变并削弱对生物力学刺激的反应

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作者:Giorgia Del Favero, Lydia Woelflingseder, Lukas Janker, Benjamin Neuditschko, Stefano Seriani, Paolo Gallina, Orfeo Sbaizero, Christopher Gerner, Doris Marko

Abstract

Morphology together with the capability to respond to surrounding stimuli are key elements governing the spatial interaction of living cells with the environment. In this respect, biomechanical stimulation can trigger significant physiological cascades that can potentially modulate toxicity. Deoxynivalenol (DON, vomitoxin) is one of the most prevalent mycotoxins produced by Fusarium spp. and it was used to explore the delicate interaction between biomechanical stimulation and cytotoxicity in A431 cells. In fact, in addition of being a food contaminant, DON is a relevant toxin for several organ systems. The combination between biomechanical stimulation and the mycotoxin revealed how DON can impair crucial functions affecting cellular morphology, tubulin and lysosomes at concentrations even below those known to be cytotoxic in routine toxicity studies. Sub-toxic concentrations of DON (0.1-1 μM) impaired the capability of A431 cells to respond to a biomechanical stimulation that normally sustains trophic effects in these cells. Moreover, the effects of DON (0.1-10 μM) were partially modulated by the application of uniaxial stretching (0.5 Hz, 24 h, 15% deformation). Ultimately, proteomic analysis revealed the potential of DON to alter several proteins necessary for cell adhesion and cytoskeletal modulation suggesting a molecular link between biomechanics and the cytotoxic potential of the mycotoxin.

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