The Effects of Gossypol on Apoptosis‐Related Gene Expression in Racially Different Triple‐Negative Breast Cancer Cells

Abstract

Apoptosis is a gene‐directed mechanism that regulates cell proliferation and maintains homeostasis. However, the uncontrolled apoptotic process can lead to several pathological conditions such as tumorigenesis, and cancer metastasis. In the current study, the apoptotic effect of the natural polyphenol compound gossypol (GOSS) was investigated in the triple negative breast cancer (TNBC) cells. The effect of GOSS was evaluated in two cell lines representing Caucasian Americans and African Americans: MDA‐MB‐231 (MM‐231) and MDA‐MB‐468 (MM‐468), respectively. In both cell lines, a similar response was noticed in both cytotoxicity and proliferation studies. However, MM‐468 cells were 3‐fold more sensitive to the apoptotic effect of the compound that was accompanied by a longer delay in the colony formation. Furthermore, GOSS was found to alter the expression of many apoptosis‐related genes in our mRNA expression investigation. The compound significantly upregulated GADD45A, TNFRSF9, and BNIP3 in MM‐231 cells. Similarly, GADD45A and BNIP3 were upregulated in MM‐468. A significant finding observed in this study is the profound 159‐fold increase in the TNF gene expression that was found in MM‐468 cells. Moreover, the apoptosis‐suppressor gene, BIRC5 was significantly repressed by more than 90% in both cell lines as well as DAPK1 in MM‐231 and TP73 in MM‐468 cells. In conclusion, the data obtained in this study can provide a more understanding of the GOSS‐induced apoptosis effect and enhance the importance of this polyphenol compound as targeted towards BC treatment, particularly in African American women.Support or Funding InformationThis research was supported by NIH NIMHD Grants G12 MD007582 and P20 MD 006738This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.