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Cancer Chemother Pharmacol. 2011 Aug;68(2):359-69. doi: 10.1007/s00280-010-1492-9. Epub 2010 Oct 27.

Conjugation of chlorin p(6) to histamine enhances its cellular uptake and phototoxicity in oral cancer cells.

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  • 1Laser Biomedical Applications and Instrumentation Division, Raja Ramanna Center for Advanced Technology, Indore, India.



Our previous studies in hamster cheek pouch model have shown that chlorin p (6) (Cp (6)), a chlorophyll derivative is a suitable photosensitizer for photodynamic treatment (PDT) of small tumors (<5 mm). However, for bigger tumors, the accumulation of Cp (6) was inadequate, which compromised the effectiveness of PDT. The purpose of present study was to investigate the possibility of improving the cellular uptake of Cp (6) by conjugating it to histamine, a biogenic amine that is known to modulate tumor growth and development via cell surface receptors.


The conjugate of Cp (6) and histamine (Cp (6)-his) was prepared by carbodiimide coupling reaction. Cellular uptake, intracellular localization and cytotoxicity of both Cp (6) and its conjugate were investigated in two human oral cancer cell lines (4451 and NT8e). The percentage of necrotic and apoptotic cells after PDT were also estimated using Hoechst 33342-propidium iodide staining.


In both the cell line, the cellular uptake of Cp (6)-his was found to be ~10 times higher when compared to Cp (6). Histamine led to a slight increase in intracellular uptake of Cp (6)-his, whereas ranitidine, a histamine H2 receptor antagonist, and incubation at lower temperature (~15°C) led to its inhibition, suggesting that uptake of Cp (6)-his is receptor mediated. Results on western blot confirmed the presence of H2 receptor in both the cell line. Observations on intracellular localization revealed that unlike Cp (6), which localized on multiple sites, Cp (6)-his showed localization on the cell membrane and around the perinuclear region. Moreover, the phototoxicity induced by Cp (6)-his was ~4 times higher when compared to Cp (6) in both the cell lines. There was, however, no significant difference in the mode of cell death.


Results suggest that conjugating Cp (6) with histamine can help improve the effectiveness of PDT in oral cancer cells by enhancing its intracellular delivery.

[PubMed - indexed for MEDLINE]
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