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Anticancer and chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa.
MedLine Citation:
PMID:  20564026     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Cycloviolacin O2 (CyO2), a cyclotide from Viola odorata (Violaceae) has antitumor effects and causes cell death by membrane permeabilization. In the breast cancer line, MCF-7 and its drug resistant subline MCF-7/ADR, the cytotoxic effects of CyO2 (0.2-10 microM) were monitored in the presence and absence of doxorubicin (0.1-5 microM) using cell proliferation assays to establish its chemosensitizing abilities. SYTOX Green assays were Sperformed to verify membrane permeabilization and showed cellular disruption correlates with cyclotide chemosensitization. Fluorescence microscopy studies demonstrated increased cellular internalization of doxorubicin in drug resistant cells when coexposed to CyO2. Interestingly, CyO2 did not produce significant membrane disruption in primary human brain endothelial cells, which suggested cyclotide specificity toward induced pore formation in highly proliferating tumor cells. Furthermore, three novel cyclotides (psyle A, C and E) from Psychotria leptothyrsa (Rubiaceae) were also monitored for cytotoxic activity. The cyclotides displayed potent cytotoxicity (IC50 = 0.64->10 microM), and coexposure to cyclotides significantly enhanced doxorubicin induced toxicity (IC50 = 0.39-0.76 microM). This study documents several cyclotides with robust cytotoxicity that may be promising chemosensitizing agents against drug resistant breast cancer.
Authors:
Samantha L Gerlach; Ramesh Rathinakumar; Geetika Chakravarty; Ulf Göransson; William C Wimley; Steven P Darwin; Debasis Mondal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biopolymers     Volume:  94     ISSN:  0006-3525     ISO Abbreviation:  Biopolymers     Publication Date:  2010  
Date Detail:
Created Date:  2011-02-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372525     Medline TA:  Biopolymers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  617-25     Citation Subset:  IM    
Affiliation:
Department of Ecology and Evolutionary Biology, Tulane University, 2863 St. Charles Avenue, 400 Boggs Center for Energy and Biotechnology, New Orleans, LA 70118, USA. sgerlach@tulane.edu
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