Purified salograviolide A isolated from centaurea ainetensis causes growth inhibition and apoptosis in neoplastic epidermal cells.
Many of the best-selling anticancer drugs are plant-derived. We tested for the anticancer properties of extracts isolated from Centaurea ainetensis, a plant species endemic to Lebanon and which is often used in folk medicine. We performed bioassay-guided fractionation of Centaurea ainetensis extracts using a panel of normal and neoplastic murine cells to identify a component that is associated with antitumor activities. Among several compounds that were fractionated, the sesquiterpene lactone, Salograviolide A, was identified and found to exert the most significant growth inhibitory effects on neoplastic cells. At concentrations that were non-cytotoxic to primary keratinocytes, Centaurea ainetensis crude extract and Salograviolide A preferentially inhibited the proliferation of papilloma and squamous cell carcinoma (SCC) cell lines without significantly affecting the growth of normal cells. Flow cytometric analysis of DNA content indicated that the inhibition of cell proliferation by Centaurea ainetensis crude extract and Salograviolide A was due to G0/G1 cell cycle arrest and increased pre-G0/G1, respectively. The increase in pre-G0/G1, and presumably apoptosis induction, in Salograviolide A-treated keratinocytes was confirmed by DNA Hoechst staining. Western blot analysis and electrophoretic mobility shift assay showed that both the crude extract and the isolated molecule differentially modulated key cell cycle and apoptotic regulators as well as NF-kappaB signaling. Salograviolide A-induced growth inhibition in neoplastic cells was mediated by the accumulation of reactive oxygen species (ROS) highlighting a potent oxidant role of this molecule. These studies suggest the potential therapeutic effects of Centaurea ainetensis, and its component, Salograviolide A, against epidermal squamous cell carcinogenesis.
Ghantous
Akram
A
Department of Biology, American University of Beirut, Beirut, Lebanon.
Tayyoun
Ahmad Abou
AA
Lteif
Ghada Abou
GA
Saliba
Najat A
NA
Gali-Muhtasib
Hala
H
El-Sabban
Marwan
M
Darwiche
Nadine
N
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D031179:Centaurea / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D006575:Heterocyclic Compounds, 3-Ring; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C528991:salograviolide A