Targeted apoptosis in ovarian cancer cells through mitochondrial dysfunction in response to Sambucus nigra agglutinin

Ovarian carcinoma (OC) patients encounter the severe challenge of clinical management owing to lack of screening measures, chemoresistance and finally dearth of non-toxic therapeutics. Cancer cells deploy various defense strategies to sustain the tumor microenvironment, among which deregulated apoptosis remains a versatile promoter of cancer progression. Although recent research has focused on identifying agents capable of inducing apoptosis in cancer cells, yet molecules efficiently breaching their survival advantage are yet to be classified. Here we identify lectin, Sambucus nigra agglutinin (SNA) to exhibit selectivity towards identifying OC by virtue of its specific recognition of α-2, 6-linked sialic acids. Superficial binding of SNA to the OC cells confirm the hyper-sialylated status of the disease. Further, SNA activates the signaling pathways of AKT and ERK1/2, which eventually promotes de-phosphorylation of dynamin-related protein-1 (Drp-1). Upon its translocation to the mitochondrial fission loci Drp-1 mediates the central role of switch in the mitochondrial phenotype to attain fragmented morphology. We confirmed mitochondrial outer membrane permeabilization resulting in ROS generation and cytochrome-c release into the cytosol. SNA response resulted in an allied shift of the bioenergetics profile from Warburg phenotype to elevated mitochondrial oxidative phosphorylation, altogether highlighting the involvement of mitochondrial dysfunction in restraining cancer progression. Inability to replenish the SNA-induced energy crunch of the proliferating cancer cells on the event of perturbed respiratory outcome resulted in cell cycle arrest before G2/M phase. Our findings position SNA at a crucial juncture where it proves to be a promising candidate for impeding progression of OC. Altogether we unveil the novel aspect of identifying natural molecules harboring the inherent capability of targeting mitochondrial structural dynamics, to hold the future for developing non-toxic therapeutics for treating OC

A manganese oxide nanozyme prevents the oxidative damage of biomolecules without affecting the endogenous antioxidant system

Biocompatible nanoparticles with an intrinsic ability to mimic the cellular antioxidant enzymes are potential candidates for the development of new therapeutics for various oxidative stress related disorders. However, the understanding of the interaction and the mechanistic crosstalk between the nanoparticles and the cellular biomolecules is limited. Here we show that the multienzyme mimic manganese(ii,iii) oxide, Mn 3 O 4 , in nanoform (Mp) rescues the cells from oxidative damage induced by reactive oxygen species (ROS). The nanoparticles provide remarkable protection to biomolecules against the ROS-mediated protein oxidation, lipid peroxidation and DNA damage. Interestingly, the endogenous antioxidant machinery remains unaltered in the presence of these nanozymes, indicating the small molecule targeting of these nanoparticles in the cellular redox modulation. This study delineates the possible mechanism by which the nanoparticles provide protection to the cells against the adverse effects of oxidative stress. Based on our observation, we suggest that the multienzyme mimic Mn 3 O 4 nanoparticles possess great potential in suppressing the oxidative stress-mediated pathophysiological conditions under which the antioxidant system is overwhelmed. This journal is © The Royal Society of Chemistry