Linked Life Data

16985057

Source:http://linkedlifedata.com/resource/pubmed/id/16985057

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-9-20
pubmed:abstractText
Despite advances in surgery, radiation, and chemotherapy, novel therapeutics are needed for head and neck cancer treatment. The objective of this current study was to evaluate alexidine dihydrochloride as a novel compound lead for head and neck cancers. Using a tetrazolium-based assay, the dose required to reduce cell viability by 50% (ED50) was found to be approximately 1.8 micromol/L in FaDu (human hypopharyngeal squamous cancer) and approximately 2.6 micromol/L in C666-1 (human undifferentiated nasopharyngeal cancer) cells. In contrast, the ED50 values were much higher in untransformed cells, specifically at approximately 8.8 micromol/L in GM05757 (primary normal human fibroblast), approximately 8.9 micromol/L in HNEpC (primary normal human nasal epithelial), and approximately 19.6 micromol/L in NIH/3T3 (mouse embryonic fibroblast) cells. Alexidine dihydrochloride did not interfere with the activities of cisplatin, 5-fluorouracil, or radiation, and interacted in a less-than-additive manner. DNA content analyses and Hoechst 33342 staining revealed that this compound induced apoptosis. Alexidine dihydrochloride-induced mitochondrial damage was visualized using transmission electron microscopy. Mitochondrial membrane potential (DeltaPsiM) depolarization was detectable after only 3 hours of treatment, and was followed by cytosolic Ca2+ increase along with loss of membrane integrity/cell death. Caspase-2 and caspase-9 activities were detectable at 12 hours, caspase-8 at 24 hours, and caspase-3 at 48 hours. FaDu cell clonogenic survival was reduced to < 5% with 1 micromol/L alexidine dihydrochloride, and, correspondingly, this compound decreased the in vivo tumor-forming potential of FaDu cells. Thus, we have identified alexidine dihydrochloride as the first bisbiguanide compound with anticancer specificity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2234-40
pubmed:meshHeading
pubmed-meshheading:16985057-Animals, pubmed-meshheading:16985057-Antineoplastic Agents, pubmed-meshheading:16985057-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:16985057-Apoptosis, pubmed-meshheading:16985057-Biguanides, pubmed-meshheading:16985057-Carcinoma, Squamous Cell, pubmed-meshheading:16985057-Caspase 2, pubmed-meshheading:16985057-Caspase 9, pubmed-meshheading:16985057-Cisplatin, pubmed-meshheading:16985057-Enzyme Activation, pubmed-meshheading:16985057-Female, pubmed-meshheading:16985057-Fluorouracil, pubmed-meshheading:16985057-Humans, pubmed-meshheading:16985057-Hypopharyngeal Neoplasms, pubmed-meshheading:16985057-Membrane Potentials, pubmed-meshheading:16985057-Mice, pubmed-meshheading:16985057-Mice, Inbred BALB C, pubmed-meshheading:16985057-Mice, SCID, pubmed-meshheading:16985057-Mitochondrial Membranes, pubmed-meshheading:16985057-NIH 3T3 Cells, pubmed-meshheading:16985057-Xenograft Model Antitumor Assays
pubmed:year
2006
pubmed:articleTitle
Potential use of alexidine dihydrochloride as an apoptosis-promoting anticancer agent.
pubmed:affiliation
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't