Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties

Alex Dayton, Karuppaiyah Selvendiran, M. Lakshmi Kuppusamy, Brian K. Rivera, Sarath Meduru, T. Kalai, K. Hideg, Periannan Kuppusamy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1027-1032
Number of pages6
JournalCancer Biology and Therapy
Volume10
Issue number10
DOIs
Publication statusPublished - Nov 15 2010

Fingerprint

Curcumin
Neoplasms
Curcuma
Rhizome
Electron Spin Resonance Spectroscopy
(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)
Intraperitoneal Injections
Heterografts
Spectrum Analysis
Stomach
Kidney
Cell Line
Liver
Growth

Keywords

  • Bioabsorption
  • Curcumin
  • HO-3867
  • Ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties. / Dayton, Alex; Selvendiran, Karuppaiyah; Kuppusamy, M. Lakshmi; Rivera, Brian K.; Meduru, Sarath; Kalai, T.; Hideg, K.; Kuppusamy, Periannan.

In: Cancer Biology and Therapy, Vol. 10, No. 10, 15.11.2010, p. 1027-1032.

Research output: Contribution to journalArticle

Dayton, Alex ; Selvendiran, Karuppaiyah ; Kuppusamy, M. Lakshmi ; Rivera, Brian K. ; Meduru, Sarath ; Kalai, T. ; Hideg, K. ; Kuppusamy, Periannan. / Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties. In: Cancer Biology and Therapy. 2010 ; Vol. 10, No. 10. pp. 1027-1032.
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