Related Experiment Video
Updated: Mar 3, 2026
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Targeted apoptosis in ovarian cancer cells through mitochondrial dysfunction in response to Sambucus nigra agglutinin
Shreya Roy Chowdhury1, Upasana Ray1, Bishnu P Chatterjee2
1Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
Abstract:
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.
Insights
Sambucus nigra agglutinin (SNA) targets ovarian cancer by binding to cancer cells, triggering mitochondrial dysfunction and cell cycle arrest. This natural lectin shows promise as a non-toxic therapeutic for ovarian carcinoma (OC).
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Ovarian carcinoma (OC) presents significant clinical challenges due to limited screening, chemoresistance, and a lack of effective, non-toxic therapeutics.
- Deregulated apoptosis is a key mechanism enabling cancer cells to survive and progress within the tumor microenvironment.
- Identifying novel agents that can overcome cancer cell survival mechanisms is crucial for developing new treatments.
Purpose of the Study:
- To identify a natural molecule that selectively targets ovarian cancer cells.
- To elucidate the mechanism by which this molecule impedes ovarian cancer progression.
- To evaluate its potential as a non-toxic therapeutic agent for ovarian carcinoma.
Main Methods:
- Utilized Sambucus nigra agglutinin (SNA) lectin for its specific recognition of α-2, 6-linked sialic acids found on OC cells.
- Investigated SNA's effects on AKT and ERK1/2 signaling pathways and dynamin-related protein-1 (Drp-1) phosphorylation.
- Analyzed mitochondrial morphology, outer membrane permeabilization, ROS generation, cytochrome-c release, and bioenergetic profile shifts (Warburg phenotype to oxidative phosphorylation).
- Assessed cell cycle progression and arrest in response to SNA treatment.
Main Results:
- SNA selectively binds to OC cells, confirming their hyper-sialylated status.
- SNA activates AKT and ERK1/2 pathways, leading to Drp-1 de-phosphorylation and mitochondrial fragmentation.
- SNA induces mitochondrial outer membrane permeabilization, cytochrome-c release, and a shift from Warburg metabolism to oxidative phosphorylation.
- This metabolic shift creates an energy deficit, causing cell cycle arrest before the G2/M phase, thereby restraining OC progression.
Conclusions:
- Sambucus nigra agglutinin (SNA) demonstrates selective targeting of ovarian cancer cells via recognition of sialic acid residues.
- SNA induces mitochondrial dysfunction and metabolic crisis, leading to cell cycle arrest and inhibition of OC progression.
- SNA represents a promising natural molecule for developing novel, non-toxic therapeutics for ovarian carcinoma by targeting mitochondrial dynamics.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:31The Intrinsic Apoptotic Pathway
01:30Apoptosis
01:17The Extrinsic Apoptotic Pathway
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...