Plumbagin Induces Cytotoxicity via Loss of Mitochondrial Membrane Potential and Caspase Activation in Metastatic Retinoblastoma

Abstract

Background/Aim: We investigated the cytotoxic effects of plumbagin on metastatic retinoblastoma, using the highly metastatic cell line Y79. Materials and Methods: Effect of plumbagin on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry with trypan blue-exclusion assay. Cell death was studied with acridine orange/ethidium bromide live-dead assay and annexin-V-fluorescein isothiocyanate/propidium iodide microscopy. Loss of mitochondrial membrane potential was studied with JC-10 dye and caspase activation was investigated using CellEvent Caspase-3/7 Green detection reagent. Results: Plumbagin highly significantly reduced the growth of Y79 cells treated for 24 h with 2.5 μM or more. Plumbagin also induced significantly high levels of cell death which was associated with loss of mitochondrial membrane potential and caspase activation. Conclusion: At very low concentration (2.5 μM), plumbagin potently induced cytotoxicity in metastatic retinoblastoma cells via loss of mitochondrial membrane potential and caspase activation.

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“…Compound 5d also induced a change in the mitochondrial membrane potential in 23.9% of cells ( Figure 4 ). Complex mitochondrial changes and alterations in the mitochondrial membrane potential may be an early event in the apoptotic process or, conversely, may be a consequence of the apoptotic signaling pathway [ 49 , 50 ]. In response to multiple distinct intracellular stress conditions, mitochondrial membranes can become permeabilized because of the pore-forming activity of the proapoptotic members of the Bcl-2 protein family.…”

“…In response to multiple distinct intracellular stress conditions, mitochondrial membranes can become permeabilized because of the pore-forming activity of the proapoptotic members of the Bcl-2 protein family. Alternatively, mitochondria can lose their structural integrity after the mitochondrial permeability transition, a phenomenon that is initiated at the mitochondrial inner membrane [ 50 , 51 ]. In both cases, permeabilized mitochondria allow the release of proapoptotic proteins into the cellular cytoplasm.…”

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