Induction of apoptosis by VB1 in breast cancer cells: The role of reactive oxygen species and Bcl-2 family proteins

Abstract

We have previously reported that the EVn-50 mixture of vitexins (lignan compounds) containing the purified vitexin (neolignan) compound, 6-hydroxy-4(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde, termed VB1, exhibits potent anticancer activity through the induction of apoptosis in several types of cancer cells, including MDA-MB-231 cells. However, the exact molecular mechanisms by which VB1 induces apoptosis in MDA-MB-231 cells have not yet been fully elucidated. In this study, to our knowledge, we provide for the first time mechanistic evidence that VB1-induced apoptosis in the human breast cancer line, MDA-MB-231, is associated with the generation of reactive oxygen species (ROS), the activation of caspases and the modulation of the expression of myeloid leukemia cell differentiation protein 1 (Mcl-1), B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins. The silencing of Mcl-1 by RNA interference enhanced VB1-induced apoptosis. In addition, VB1 did not induce ROS generation or apoptosis in the immortalized non-cancerous breast cell line, MCF-10A. Our findings reveal a novel mechanism underlying VB1-induced apoptosis, and highlight VB1 as a promising candidate for the therapy of human breast cancer.