Luteolin inhibits DNA methyltransferase 1 and alpha 6-integrin gene expression to suppress proliferation and stemness in breast cancer cells from patients of West African ancestry

Breast cancer mortality remains disproportionately high among women of West African (WA) ancestry, a disparity influenced in part by biological differences that shape how tumors behave and respond to treatment. We evaluated the ability of luteolin (a naturally occurring flavonoid) to confer anticancer actions in breast cancer cell lines from patients of WA and European ancestries. In estrogen receptor-positive (ER+) breast cancer cells, including those resistant to the anti-estrogen fulvestrant and triple-negative breast cancer (TNBC) models, luteolin reduced proliferation and impaired mammosphere formation. Our data suggest that luteolin can provide an alternative or complementary approach to treat breast cancer, irrespective of subtype. Notably, breast cancer cells from patients of WA ancestry demonstrated heightened sensitivity to luteolin's antiproliferative and anti-stemness effects, suggesting potential ancestry-related therapeutic vulnerabilities. Because the elevated stemness-associated molecules DNA methyltransferase 1 (DNMT1) and alpha-6 integrin (ITGA6) are both linked to poor outcomes and disease aggressiveness, we examined their regulation following luteolin treatment. Luteolin decreased the expression levels of DNMT1 and ITGA6. These findings suggest that luteolin and other natural products have the potential to help thwart drivers of aggressive breast cancer and improve breast cancer survival among patients of West African ancestry.