title: 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.
authors.affiliation: The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Zhou
authors.affiliation: The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ding
authors.affiliation: The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Shun-Zhi
authors.initials: SZ
authors.lastname: Zhang
authors.affiliation: The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Sun
authors.affiliation: Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Cao
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D020868:Gene Silencing; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D017705:Lignans; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D047310:Apigenin; C032731:vitexin; D020169:Caspases