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bioRxiv · 10.1101/2024.10.21.619400

Comparative study of Ergosterol and 7-dehydrocholesterol and their Endoperoxides: Generation, Identification and Impact in Phospholipid Membranes and Melanoma Cells

Yukuyama, M. N.·Fabiano, K. C.·Inague, A.·Uemi, M.·Lima, R. S.·Diniz, L. R.·Oliveira, T. E.·Iijima, T. S.·Faria, H. O. F.·Santos, R. S.·Nolf, M. F. V.·Chaves-Filho, A. B.·Yoshinaga, M. Y. B.·Junqueira, H. C.·Di Mascio, P.·Baptista, M. d. S.·Miyamoto, S.
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Abstract

Melanoma is an aggressive cancer that has attracted attention in recent years due to its high mortality rate of 80%. Damage caused by oxidative stress generated by radical (type I reaction) and singlet oxygen, 1O2 (type II reaction) oxidative reactions may induce cancer. Thus, studies that aim to unveil the mechanism that drives these oxidative damage processes become relevant. Ergosterol, an analogue of 7-dehydrocholesterol, important in the structure of cell membranes, is widely explored in cancer treatment. However, to date little is known about the impact of different oxidative reactions on these sterols in melanoma treatment, and conflicting results about their effectiveness complicates the understanding of their role in oxidative damage. Our results highlight differences among ergosterol, 7-dehydrocholesterol (7-DHC) and cholesterol in membrane properties when subjected to distinct oxidative reactions. Furthermore, we conducted a comparative study exploring the mechanisms of cell damage by photodynamic treatment in A375 melanoma. Notably, endoperoxides from ergosterol and 7-DHC generated by 1O2 showed superior efficacy in reducing the viability of A375 cells compared to their precursor molecules. We also describe a step-by-step process to produce and identify endoperoxides derived from ergosterol and 7-DHC. While further studies are needed, this work provides new insights for understanding cancer cell death induced by different oxidative reactions in the presence of biologically relevant sterols.

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Yukuyama, M. N., Fabiano, K. C., Inague, A., Uemi, M., Lima, R. S., Diniz, L. R., Oliveira, T. E., Iijima, T. S., Faria, H. O. F., Santos, R. S., Nolf, M. F. V., Chaves-Filho, A. B., Yoshinaga, M. Y. B., Junqueira, H. C., Di Mascio, P., Baptista, M. d. S., Miyamoto, S.. 2024-10-24. Comparative study of Ergosterol and 7-dehydrocholesterol and their Endoperoxides: Generation, Identification and Impact in Phospholipid Membranes and Melanoma Cells. https://doi.org/10.1101/2024.10.21.619400

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