Document Detail

Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties.
MedLine Citation:
PMID:  20798598     Owner:  NLM     Status:  MEDLINE    
Curcumin, a naturally-occurring compound found in the rhizome of Curcuma longa plant, is known for its antitumor activities. However, its clinical efficacy is limited due to poor bioabsorption. A new class of synthetic analogs of curcumin, namely diarylidenylpiperidone (DAP), has been developed with substantially higher anticancer activity than curcumin. However, its cellular uptake and bioabsorption have not been evaluated. In this study we have determined the absorption of a representative DAP compound, HO-3867, using optical and electron paramagnetic resonance spectrometry. The cellular uptake of HO-3867 was measured in a variety of cancer cell lines. HO-3867 was taken in cells within 15 minutes of exposure and its uptake was more than 100-fold higher than curcumin. HO-3867 was also retained in cells in an active form for 72 hours and possibly longer. HO-3867 was substantially cytotoxic to all the cancer cells tested. However, there was no direct correlation between cellular uptake and cytotoxicity suggesting that the cytotoxic mechanisms could be cell-type specific. When administered to rats by intraperitoneal injection, significantly high levels of HO-3867 were found in the liver, kidney, stomach, and blood after 3 hours. Also, significant accumulation of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition of tumor growth. The results suggest that the curcumin analog has substantially higher bioabsorption when compared to curcumin.
Alex Dayton; Karuppaiyah Selvendiran; M Lakshmi Kuppusamy; Brian K Rivera; Sarath Meduru; Tamás Kálai; Kálmán Hideg; Periannan Kuppusamy
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-15
Journal Detail:
Title:  Cancer biology & therapy     Volume:  10     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-03-10     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1027-32     Citation Subset:  IM    
Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, USA.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Curcumin / therapeutic use*
Electron Spin Resonance Spectroscopy
Mice, Inbred BALB C
Mice, Nude
Ovarian Neoplasms / drug therapy*
Piperidones / pharmacokinetics*,  therapeutic use*
Rats, Wistar
Tissue Distribution
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/(3,5-bis((4-fluorophenyl)methylidene)-1-((1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl)piperidin-4-one); 0/Antineoplastic Agents; 0/Piperidones; 458-37-7/Curcumin

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