Webb, R. J. | bioRxiv Science

bioRxiv2026

Na+/K+-ATPase Blockade Reversibly Attenuates Proliferation and Metabolic Function in K562 Human Myelogenous Leukemia Cells

The Na+/K+-ATPase consumes a substantial portion of cellular ATP to maintain essential electrochemical gradients, yet its role in regulating cancer cell proliferation and phenotypic plasticity remains complicated by its dual function as an ion transporter and a scaffolding receptor. Here, we investigate the physiological consequences of pharmacological NKA blockade using digoxin in K562 human chronic myelogenous leukemia cells. Submicromolar digoxin exposure induced a concentration-dependent attenuation of cell proliferation (IC50 = 151.0 nM) and a statistically significant depression of metabolic reducing capacity without impairing cell viability. Competitive supplementation with extracellular potassium salts produced a surmountable rightward shift in digoxin sensitivity, confirming that growth inhibition is driven by on-target NKA pump occupancy rather than non-specific interactions. Furthermore, this cytostatic growth attenuation and metabolic depression were found to be fully reversible upon drug clearance. K562 cells are largely refractory to canonical kinase-overdrive stress checkpoints as they harbor constitutive BCR-ABL tyrosine kinase activity alongside non-functional TP53 and a homozygous deletion of CDKN2A (p16INK4a). Consequently, these findings suggest that NKA perturbation attenuates K562 growth primarily through ion dyshomeostasis and secondary active transport constraints rather than scaffold-mediated signaling. Overall, we present a novel model for elucidating the role of the NKA in cancer proliferation and dissecting the mechanistic underpinnings of ion-mediated alterations in cancer cell physiology.

cancer biology↗

bioRxiv2026

Glutathione impacts both Batrachochytrium dendrobatidis virulence and amphibian cellular defence in a chytridiomycosis model

Glutathione has important roles in diverse infections, yet its involvement in the interaction between the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd) and its amphibian hosts is still unclear. Using in vitro assays and a cell infection model, we examined how glutathione influences Bd virulence traits and cellular host disease resistance. For Bd, inhibition of glutathione reductase rapidly killed zoospores, indicating that glutathione is essential for this pathogen. In addition, exposure to exogenous glutathione promoted the potential for virulence through accelerated and increased zoospore release. In host amphibian cells, Bd infection decreased intracellular glutathione content and increased reactive oxygen species, suggesting that chytridiomycosis pathogenesis may involve oxidative stress. Depletion of host glutathione before exposure to Bd increased infection severity and Bd growth, whereas amphibian cells with slightly elevated glutathione levels were partially protected against Bd. However, manipulation of host glutathione levels after the establishment of Bd infection did not impact its intracellular growth, implying that the host glutathione-mediated resistance only occurs during the initial Bd invasion process. Importantly, this effect of glutathione on host resistance is not a general response to pathogens, as it was not observed in cells exposed to viral pathogen FV3. As glutathione increased both infectious zoospore production and host resistance to zoospore infection, our study suggests that this antioxidant may play an important role in the host/pathogen interaction during chytridiomycosis. Thus, environmental conditions and therapeutic approaches that affect glutathione systems in the host and/or pathogen have the potential to alter chytridiomycosis dynamics and should be further explored.

pathology↗