Nobiletin inhibits breast cancer via p38 mitogen-activated protein kinase, nuclear transcription factor-κB, and nuclear factor erythroid 2-related factor 2 pathways in MCF-7 cells

Food Nutr Res. 2018 Nov 21:62. doi: 10.29219/fnr.v62.1323. eCollection 2018.

Abstract

Introduction: Breast cancer is one of the most commonly diagnosed cancers in women, with a high mortality rate.

Objective: In the present study, we evaluated the anticancer effect of nobiletin, a flavone glycoside, on the breast cancer cell line MCF-7.

Result: Cell viability and proliferation decreased and cell morphology changed from diamond to round after being treated with nobiletin. Nobiletin induced apoptosis of breast cancer MCF-7 cells via regulating the protein expression of Bax, Bcl-2, cleaved caspase-3, and p53. The expression of Bcl-2 decreased, while the expression of Bax and p53 increased in MCF-7 cells treated with nobiletin. Meanwhile, nobiletin inhibited cell migration by downregulating the protein expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Moreover, phosphorylation of p38 was increased, and the translocation of p65 and nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus was decreased, which suggested that the anticancer effects of nobiletin might at least partially rely on mediating the p38 mitogen-activated protein kinase, nuclear transcription factor-κB, and Nrf2 pathways in MCF-7 breast cancer cells.

Conclusion and recommendation: Our data showed that nobiletin was a potential antitumor drug, and it provided some experimental basis for the clinical application of tumor therapy.

Keywords: anticancer; apoptosis; breast cancer MCF-7 cells; cell signaling pathway; nobiletin.