The Potent Antioxidant 3,5-Dihydroxy-4-Methoxybenzyl Alcohol Reveals Anticancer Activity by Targeting Several Signaling Pathways in Bone Metastatic Human Breast Cancer MDA-MB-231 Cells

Abstract

Human breast cancer is the leading cause of cancer-related death in women. Bone metastatic human breast cancer MDA-MB-231 cells are triple negative. The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a potent antioxidant, has been shown to prevent oxidative stress by scavenging free radicals in cells. This study investigates the effects of DHMBA on MDA-MB-231 cells in vitro. MDA-MB-231 cells were cultured with DHMBA (0.1–100 μM). DHMBA blocked the growth and stimulated the death of MDA-MB-231 cells, resulting in reduced cell numbers. DHMBA treatment decreased PI3-kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR and increased p53, p21, and Rb, which are suppressors in cell growth. DHMBA inhibited metastatic activity, including adhesion and migration of MDA-MB-231 cells. Coculture with MDA-MB-231 cells resulted in decreased growth and stimulated death of osteoblastic MC3T3-E1 cells and macrophage RAW264.7 cells, suggesting that cancer cells affect the bone microenvironment. Production of TNF-α, which is the mediator in the bone microenvironment, in MDA-MB-231 cells was inhibited by DHMBA treatment. Crosstalk between cancer cells and cells in the bone microenvironment was blocked by culture with DHMBA. DHMBA may inhibit the activity of triple-negative human breast cancer cells, providing a useful tool for the treatment of breast cancer.