Related Experiment Video
Updated: Jan 20, 2026
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70
Alessandra Russo1, Venera Cardile2, Rosanna Avola2
1Department of Drug Sciences, University of Catania, Catania, Italy.
Abstract:
Isocordin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively. These analogues, 4, 5, and 6, also induced an apoptotic response at 12.5- and 25-μM concentrations. They inhibited the expression of antiapoptotic proteins Bcl-2 and Hsp70, a critical factor that promotes tumour cell survival. In contrast, Bax and caspase-9 expression, and caspase-3 enzyme resulted activated. These results were correlated to a DNA fragmentation typical of apoptosis and an increase of intracellular reactive oxygen species (ROS) levels. Alternatively, at higher concentration (50 μM), when the capacity of the cells to sustain Hsp70 synthesis is reduced, our results seem to indicate that necrosis was induced by a further increase in ROS production. Therefore, the central finding in the present study is that these molecules downregulates Hsp70 expression. Altogether, these results suggest that 4-oxyalkyl-isocordoin analogues 4, 5, and 6 deserve to be deeply investigated for a possible application as Hsp70 inhibitor in the management of melanoma.
Insights
New isocordoin analogues show potent anti-melanoma activity by downregulating heat shock protein 70 (Hsp70). These compounds induce apoptosis and may offer a novel therapeutic strategy for melanoma management.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Pharmacology
Background:
- Melanoma is an aggressive skin cancer with limited treatment options.
- Heat shock protein 70 (Hsp70) is a key factor in tumor cell survival and resistance to therapy.
Purpose of the Study:
- To evaluate the cytotoxicity of isocordin 1 and its novel 4-oxyalkyl-isocordoin analogues against human melanoma cells.
- To investigate the molecular mechanisms underlying the observed anti-melanoma effects, focusing on apoptosis induction and Hsp70 modulation.
Main Methods:
- Cytotoxicity assays were performed on A2058 human melanoma cells.
- Apoptosis induction was assessed by evaluating protein expression (Bcl-2, Hsp70, Bax, caspase-9, caspase-3) and DNA fragmentation.
- Intracellular reactive oxygen species (ROS) levels were measured.
Main Results:
- Analogues 4, 5, and 6 exhibited significant inhibitory activity against melanoma cells (IC50 values as low as 11.62 μM).
- These analogues induced apoptosis by downregulating anti-apoptotic proteins (Bcl-2, Hsp70) and activating pro-apoptotic markers (Bax, caspase-9, caspase-3).
- Increased ROS levels were observed, potentially leading to necrosis at higher concentrations.
Conclusions:
- 4-oxyalkyl-isocordoin analogues 4, 5, and 6 demonstrate promising anti-melanoma properties.
- The primary mechanism involves the downregulation of Hsp70, suggesting its potential as a therapeutic target.
- These compounds warrant further investigation for melanoma treatment development.
More Related Videos
Related Concept Videos
10:03Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
03:52Experimental Metastatic Melanoma Mouse Model: A Platform to Study the Metastatic Potential of Melanoma Cells in the Lungs
06:55Transient Treatment of Human Pluripotent Stem Cells with DMSO to Promote Differentiation
07:42Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:41A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
05:40Melanoma Stem Cell Isolation: A Method to Obtain CD133 Positive and Negative Melanoma Cells Using Magnetic-activated Cell Sorting