The role of GAPDH in the selective toxicity of CNP in melanoma cells

GAPDH在CNP对黑色素瘤细胞选择性毒性中的作用

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作者:Claudia von Montfort, Elif Aplak, Lara Ebbert, Chantal-Kristin Wenzel, Niklas P Klahm, Wilhelm Stahl, Peter Brenneisen

Aim

Cancer cells often show an increased glycolytic rate (Warburg effect), therefore we focused on CNP mediated changes of the glucose metabolism.

Background

Malignant melanoma is the most aggressive form of skin cancer with a rather poor prognosis. Standard chemotherapy often

Conclusion

We identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a target protein for CNP mediated thiol oxidation.

Results

It has been shown before that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity is regulated via oxidation of a cysteine in the active center of the enzyme with a subsequent loss of activity. Upon CNP treatment, formation of cellular lactate and GAPDH activity were significantly lowered. The treatment of melanoma cells and melanocytes with the GAPDH inhibitor heptelidic acid (HA) decreased viability to a much higher extent in the cancer cells than in the studied normal (healthy) cells, highlighting and supporting the important role of GAPDH in cancer cells.

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