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Toxicity and phototoxicity of Hypocrellin A on malignant human cell lines, evidence of a synergistic action of photodynamic therapy with Imatinib mesylate.

Abstract
Photodynamic therapy combines a photosensitizer, localised preferentially in malignant cells with light activation. Hypocrellin A (HA), a lipid-soluble peryloquinone, is considered as a high potential photosensitizer. We report dose and light irradiation effects of HA on HeLa, Calu and K562 cell lines, the latter including a subclone resistant to Imatinib mesylate (IM, Gleevec). All cell lines and subclones tested are sensitive to HA PDT. In the epithelial tumour cell lines, we observe a significant photosensitizing effect in the presence of HA. In the leukemic K562 cells, HA exposure led to an inhibitory effect, which was not seen in the K562 cells resistant to Imatinib mesylate. However, experiments using IM and HA led to a reversal of IM-resistant phenotype in this cell line, with evidence of a major sensitizing effect of photodynamic therapy. Overall our results suggest a phototoxicity of HA in epithelial cell lines and demonstrate for the first time, a synergy between IM and photodynamic therapy to circumvent IM-resistance.
AuthorsSirinart Chio-Srichan, Noufissa Oudrhiri, Annelise Bennaceur-Griscelli, Ali G Turhan, Paul Dumas, Matthieu Refregiers
JournalJournal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 99 Issue 2 Pg. 100-4 (May 03 2010) ISSN: 1873-2682 [Electronic] Switzerland
PMID20347325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Benzamides
  • Photosensitizing Agents
  • Piperazines
  • Pyrimidines
  • Quinones
  • Phenol
  • Perylene
  • Imatinib Mesylate
  • hypocrellin A
Topics
  • Antineoplastic Agents (pharmacology)
  • Benzamides
  • Cell Line, Tumor
  • Drug Synergism
  • Drug Therapy, Combination
  • HeLa Cells
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Perylene (analogs & derivatives, chemistry, toxicity)
  • Phenol
  • Photochemotherapy
  • Photosensitizing Agents (chemistry, toxicity)
  • Piperazines (pharmacology)
  • Pyrimidines (pharmacology)
  • Quinones (chemistry, toxicity)

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