Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism

Michela Codini
ORCID logo ,
Federico Fiorani
,
Martina Mandarano
,
Samuela Cataldi
,
Cataldo Arcuri
ORCID logo ,
Alessandra Mirarchi
,
Maria Rachele Ceccarini
ORCID logo ,
Tommaso Beccari
ORCID logo ,
Toshihide Kobayashi
,
Nario Tomishige
,
Angelo Sidoni
,
Elisabetta Albi
*
Version 1 : Received: 12 June 2023 / Approved: 13 June 2023 / Online: 13 June 2023 (02:41:51 CEST)

How to cite: Codini, M.; Fiorani, F.; Mandarano, M.; Cataldi, S.; Arcuri, C.; Mirarchi, A.; Ceccarini, M.R.; Beccari, T.; Kobayashi, T.; Tomishige, N.; Sidoni, A.; Albi, E. Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism. Preprints 2023, 2023060861. https://doi.org/10.20944/preprints202306.0861.v1 Codini, M.; Fiorani, F.; Mandarano, M.; Cataldi, S.; Arcuri, C.; Mirarchi, A.; Ceccarini, M.R.; Beccari, T.; Kobayashi, T.; Tomishige, N.; Sidoni, A.; Albi, E. Vitamin C Modifies the Phenotype of Hormone Receptor Positive/HER2 Negative Breast Cancer Cells and Induces Changes in Sphingolipid Metabolism. Preprints 2023, 2023060861. https://doi.org/10.20944/preprints202306.0861.v1

Abstract

The effect of the antioxidant vitamin C in cancer has been studied for over 30 years with conflict-ing results ranging from total absence of effect, to possible protective effect, to potential therapeutic effect when administered in high doses. The aim of the study was to define the effect of vitamin C in breast cancer and the possible involvement of sphingomyelin metabolism. Therefore, the effect of low and high dose of vitamin C on cells reproducing luminal A type (MCF7) and triple negative type (MB231) of breast cancer was analyzed. The results showed that high dose of vitamin C produced effects only in MCF7 cells such as decreased cell viability, modulation of cell cycle re-lated genes, unexpected change in cell phenotype due to estrogen receptor downregulation, catabo-lism of sphingomyelin with a large increase in ceramide. In conclusion, we demonstrated that high doses of VitC on the one hand reduce the growth of lu-minal A type breast cancer cells and on the other hand induce their phenotypic change towards hormone therapy resistant cells. The effect of vitamin C on therapeutic treatment failure of luminal A breast cancer and the possible involvement of high ceramide levels were discussed.

Keywords

vitamin C; breast cancer; MCF7 cells; MB-231 cells; estrogen receptor; progesterone receptor; HER-2; Ki-67; sphingomyelin; ceramide

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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