title: Ambiguine I Isonitrile fromFischerella ambiguaInduces Caspase-Independent Cell Death in MCF-7 Hormone Dependent Breast Cancer Cells.
abstract: Ambiguine I isonitrile (AmbI) obtained from the cultured cyanobacteriumFischerella ambiguawas identified as a potent NF-κB inhibitor (IC50=30 nM). The cytotoxic effect was evaluated in both HT-29 colon cancer cell line (EC50=4.35 μM) and MCF-7 breast cancer cell line (EC50=1.7 μM) using the SRB assay. In the cells treated with AmbI, an increased population of cells was detected in sub G1-phase. The apoptotic effect was associated with block in G1-phase of the cell cycle in treated cells; however, cell death was induced independently of caspase-7. The NF-κB expression of p50 and p65 units were also examined in treated cells and compared with the positive control, rocaglamide (IC50=75 nM). Moreover, the expression of mediators of the NF-κB pathway such as kinase IKKκ was studied at increasing concentrations of AmbI. The down stream effect of NF-κB inhibition and the effect on the expression of TNF-α induced ICAM-1 was evaluated. Thus, the dose-dependent and time-dependent effect of AmbI on MCF-7 cells was examined in an attempt to investigate its potential mechanism of action on inducing apoptosis.
authors.affiliation: Division of Pharmacy Practice and Administration and Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12 Avenue, Columbus, OH 43210.
authors.forename: Ulyana Muñoz
authors.initials: UM
authors.lastname: Acuña
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Zi
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Orjala
authors.affiliation: Division of Pharmacy Practice and Administration and Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12 Avenue, Columbus, OH 43210.
authors.forename: Esperanza J
authors.initials: EJ
authors.lastname: Carcache de Blanco
keywords: Ambiguine I isonitrile; MCF-7; NF-κB; ROS; apoptosis; caspase-independent; mitochondria