PRIMA-1MET Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells

Shadi N Kotob; Jessica L Kelts

doi:10.1021/acsomega.3c03719

PRIMA-1^MET Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells

ACS Omega. 2023 Aug 8;8(33):30500-30507. doi: 10.1021/acsomega.3c03719. eCollection 2023 Aug 22.

Authors

Shadi N Kotob¹, Jessica L Kelts¹

Affiliation

¹ Department of Natural Sciences, University of Michigan-Flint, Flint, Michigan 48502, United States.

Abstract

Vitamin D is a steroid hormone that causes growth suppression in cultured cells. We had previously discovered that the triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 did not have growth suppression with vitamin D, while MCF-7 did. MCF-7 cells are not triple-negative and have wild-type p53. Both MDA-MB-231 and MDA-MB-468 have mutations in p53 and these mutations were a possible explanation for the lack of growth suppression with vitamin D. Our hypothesis was that reactivation of p53 in the triple-negative cell lines would cause them to become sensitive to vitamin D. We chose to use the small molecule PRIMA-1^MET to reactivate p53 as it has been previously shown to restore function to the p53 mutants present in MB-231 and MB-468. We then measured the ability of vitamin D and its analogues calcipotriol and EB1089 to suppress growth in the presence of PRIMA-1^MET. Here, we show that while PRIMA-1^MET can kill the breast cancer cells investigated in this study, it does not restore their sensitivity to vitamin D or its analogues.