Damnacanthal Suppresses Breast Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest via NF-ĸB Signaling

Abstract

Breast cancer is the most common cancer diagnosed and the leading cause of death for women worldwide. Noni (Morinda citrifolia L.) contains an anthraquinone called damnacanthal (3-hydroxy-1-methoxy-anthraquinone-2-aldehyde), which is known to inhibit the growth of many types of cancer cells. The purpose of this study is to examine the anticancer effects of damnacanthal on cell proliferation, apoptosis, and cell cycle in breast cancer cells and its underlying signaling pathway, including nuclear factor kappa B (NF-ĸB), epidermal growth factor receptors (EGFR), and PI3K/AKT/PTEN. Damnacanthal reduced cell viability in both normal and triple-negative breast cancer cell lines, MCF-7 and MDA-MB-231, respectively. In MCF-7 cells, damnacanthal induced late apoptosis and increased cell cycle arrest in the G0/G1 and S phase, decreased RELA gene expression, and enhanced TNF-α gene expression. However, it had no effect on the protein expression of PI3K/AKT. Damnacanthal exerted anticancer activity on MCF-7 cell lines via blocking NF-ĸB (subunit p65) expression at mRNA levels in the PI3K/AKT-independent manner. These findings highlight the potential benefits of damnacanthal as a promising NF-ĸB inhibitor for cancer prevention or treatment against breast carcinoma.