MS-275 derivative

Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [FOLR1], solute carrier [SLC]-19A1, and SLC46A1) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of SLC46A1. These inhibitors downregulated SLC19A1 expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. HDAC1/2 knockdown upregulated FOLR1 and SLC46A1 levels, whereas HDAC1/3 knockdown downregulated FOLR1 levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.

RETRACTION: G. Di Bernardo, N. Alessio, C. Dell'Aversana, F. Casale, D. Teti, M. Cipollaro, L. Altucci, and U. Galderisi, “Impact of Histone Deacetylase Inhibitors SAHA and MS‐275 on DNA Repair Pathways in Human Mesenchymal Stem Cells,” Journal of Cellular Physiology 225, no. 2 (2010): 537‐544, https://doi-org.libproxy1.nus.edu.sg/10.1002/jcp.22236.The above article, published online on 17 March 2024 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor‐in‐Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed unambiguous image manipulation in Figure 3, SAHA ‐ H2O2 Treatment and SAHA – Untreated panels. The authors admitted to these image alterations, cooperated with the investigation, and were able to provide partial raw data of the article including some of the original, unmodified images. Nonetheless, the modification of the images to change the appearance is clearly against the ethical policy of the journal and Wiley's Best Practice Guidelines on Research Integrity and Publishing Ethics. In addition, based on the received partial raw data, regarding the positive cell counts for the 8oxodG assay, the journal team could not exclude that the visual modification of these images affects the number of counted 8oxodG‐positive cells, and consequently the related conclusions of the article. Therefore, the editors have lost confidence in the data presented and have decided to retract the article. The authors were informed of the decision to retract but did not agree to the retraction.