Curcumin Induces Apoptosis by regulating the cell cycle proteins in MDA‐MB‐231 Breast CancerCells

BackgroundCurcumin, a natural polyphenolic compound found in turmeric, has potential cancertreatment efficacy, including apoptosis‐induction, in many cancer cell types. Cancer cells arecharacteristically anti‐apoptotic, highly proliferative andcontinue to live indefinitely. Controlof cell cycle progression and the initiation of apoptosis in breast cancercells is considered to be a potentially effective strategy for the prevention/treatment of the disease. The triple‐negative breast cancer cell line MDA‐MB‐231 does not express progesterone, estrogen, or human epidermal growth factor receptors, is highly aggressive and is difficult to treat. This study aims to elucidate the mechanism of curcumin‐induced apoptosis and its effects on cell cycle proteins in the MDA‐MB‐213 breast cancer cell line.MethodsApoptosis was measured by flow cytometric analysis of AnnexinV/Propidium Iodide expression. Cell cycle arrest was measured by Western Blot analyses of p21Waf‐1, p53 and retinoblastoma protein pRb, as well as the cyclin dependent kinases Cyclin B1, and Cyclin D1.ResultsFlow cytometry data suggest that curcumin induces both early and late stage apoptosis in MDA‐MB‐231 cells. Cell cycle inhibitory protein p21Waf‐1 was significantly increased in curcumin‐treated cells compared to untreated cells. Tumor suppressor protein p53 and Cyclin D1 were significantly down‐regulated (p=.0.0001 and p=0.014, respectively), pRb, another tumors uppressor protein, was unchanged, and Cyclin B1 was upregulated (p=0.0006).ConclusionGiven that upregulation of p21Waf‐1 can lead to apoptosis and can disrupt CDKs/cyclin complexes necessary for cell cycle progression, and that down‐regulation of Cyclin D1, which is required for progression through the G1/S phase and whose over expression is associated with most breast cancers, can lead to cell‐cycle arrest at G1, curcumin appears to be effective in both apoptosis induction, demonstrated also in the flow cytometric results, and in cell‐cycle arrest at G1. The upregulation of cyclinB1, which is involved in the G2/M phase transition, and the down‐regulation ofp53 by curcumin, indicate that additional mechanisms are involved with curcumin exposure. Our findings will aid in the development of future therapeutic strategies, including curcumin as a novel treatment supplement, to effectively induce both cell‐cycle arrest and apoptosis in breast tumors.Disclaimer: The views expressed in this manuscript are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or U.S. Government.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.