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.
Biomass of food yeast Kluyveromyces fragilis (MTCC 188) grown on deproteinized whey supplemented with 0.8% diammonium hydrogen phosphate and 10 ppm indole-3-acetic acid, had a crude protein content of 37%. The true protein content based on nitrogen fractionation procedure was 28.1%. Total nucleic acid content was 4.82%. This amount does not appear to be toxicologically offensive. Crude fiber, ash, and lipid content of K.fragilis dry cells were found to be 4.9%, 16%, and 7.8%, respectively. Essential fatty acids of both omega-3 and omega-6 series were found present in the fat of the yeast and represented 21.5% of the total fatty acids. All the essential amino acids were present in the proteins of K. fragilis; however, sulfur containing amino acids were found in lower amounts. Calculated protein scores indicate moderate biological value. B vitamins in the biomass were present as expected, but folic acid and pyridoxine were present in high concentration.
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