title: Plumbagin reduces human colon cancer cell survival by inducing cell cycle arrest and mitochondria-mediated apoptosis.
abstract: Despite increased use of early detection methods and more aggressive treatment strategies, the worldwide incidence of colorectal cancer is still on the rise. Consequently, it remains urgent to identify novel agents with enhanced efficacy in prevention and/or therapeutic protocols. Our studies focused on the use of Plumbagin, a natural phytochemical that showed promising results against other tumor types, to determine its effectiveness in blocking the proliferation and survival of colon cancer cells in experimental protocols mimicking the environment in primary tumors (attached culture conditions) and in circulating tumor cells (unattached conditions). Under both experimental settings, exposure of HCT116 cells to Plumbagin concentrations in the low micromolar range resulted in cell cycle arrest at the G1 phase, apoptosis via the mitochondrial cell death pathway, and increased production of reactive oxygen species. The cell cycle effects were more noticeable in attached cells, whereas the induction of cell death was more evident in unattached cells. These effects were consistent with the nature and the magnitude of the alterations induced by Plumbagin on the expression levels of a set of proteins known to play key roles in the regulation of cell cycle dynamics, apoptosis mechanisms and cell proliferation. In light of its previously reported lack of toxicity on normal colon cells and the striking anti-survival effect on colon cancer cells observed in our study, Plumbagin should be considered a promising drug for the treatment of colon cancer.
authors.affiliation: School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala-686560, India.
authors.forename: Binil
authors.initials: B
authors.lastname: Eldhose
authors.affiliation: Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Gunawan
authors.affiliation: Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Mahbubur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala-686560, India.
authors.forename: Mukalel S
authors.initials: MS
authors.lastname: Latha
authors.affiliation: Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Notario
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009285:Naphthoquinones / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C014758:plumbagin
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