Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan;34(1):173-183.
doi: 10.1002/ptr.6513. Epub 2019 Sep 12.

Coriolus versicolor-derived protein-bound polysaccharides trigger the caspase-independent cell death pathway in amelanotic but not melanotic melanoma cells

Małgorzata Pawlikowska  1 , Jakub Piotrowski  1 , Tomasz Jędrzejewski  1 , Wiesław Kozak  1 , Andrzej T Slominski  2   3 , Anna A Brożyna  4
Affiliations

Coriolus versicolor-derived protein-bound polysaccharides trigger the caspase-independent cell death pathway in amelanotic but not melanotic melanoma cells

Małgorzata Pawlikowska et al. Phytother Res. 2020 Jan.

Abstract

We have investigated the potential cell death mechanism promoted by Coriolus versicolor fungus-derived protein-bound polysaccharides (PBPs) in melanoma cells. Knowing that melanogenesis has the potential to affect the tumor behavior and melanoma therapy outcome, the cytotoxic effects of PBPs were evaluated in human SKMel-188 melanoma cell line, whose phenotype, amelanotic versus pigmented, depends on the concentration of melanin precursors in the culture medium. Our results showed that inhibitory effect of PBPs (100 and 200 μg/ml) towards melanoma cells is inversely associated with the pigmentation level. This cytotoxicity induced in nonpigmented melanoma cells by PBPs was caspase-independent; however, it was accompanied by an increased intracellular reactive oxygen species (ROS) generation. The ROS production was controlled by c-Jun N-terminal kinase (JNK) because SP600125, a JNK inhibitor, significantly reduced ROS generation and protected cells against PBPs-induced death. We also found that PBPs-induced lactate dehydrogenase release in amelanotic melanoma cells was abolished by co-treatment with receptor-interacting serine/threonine-protein kinase 1 inhibitor, implying engagement of this kinase in PBPs-induced death pathway. The results suggest that PBPs induce an alternative programmed cell death, regulated by receptor-interacting protein-1 and ROS and that this process is modified by melanin content in melanoma cells. These findings are remarkable when considering the use of commercially available Coriolus versicolor by patients who suffer from melanoma cancer.

Keywords: ROS; caspase-independent cell death; melanin; melanoma cells, necroptosis; protein-bound polysaccharides.

PubMed Disclaimer

References

REFERENCES

    1. Brenner, M., & Hearing, V. J. (2008). The protective role of melanin against UV damage in human skin. Photochem Photobiol, 84(3), 539-549. https://doi.org/10.1111/j.1751-1097.2007.00226.x
    1. Bröker, L. E., Kruyt, F. A., & Giaccone, G. (2005). Cell death independent of caspases: A review. Clin Cancer Res, 11(9), 3155-3162. https://doi.org/10.1158/1078-0432.CCR-04-2223
    1. Brozyna, A. A., Jozwicki, W., Carlson, J. A., & Slominski, A. T. (2013). Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma. Hum Pathol, 44(10), 2071-2074. https://doi.org/10.1016/j.humpath.2013.02.022
    1. Brozyna, A. A., Jozwicki, W., Roszkowski, K., Filipiak, J., & Slominski, A. T. (2016). Melanin content in melanoma metastases affects the outcome of radiotherapy. Oncotarget, 7(14), 17844-17853.
    1. Brozyna, A. A., VanMiddlesworth, L., & Slominski, A. T. (2008). Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy. Int J Cancer, 123(6), 1448-1456. https://doi.org/10.1002/ijc.23664