Poiroux, G;
Pitié, M;
Culerrier, R;
Lafont, E;
Ségui, B;
Van Damme, EJ;
Peumans, WJ;
... Benoist, H; + view all
(2011)
Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
PLoS One
, 6
(8)
, Article e23315. 10.1371/journal.pone.0023315.
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Abstract
Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy.
| Type: | Article |
|---|---|
| Title: | Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0023315 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0023315 |
| Language: | English |
| Additional information: | © 2011 Poiroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3157357 |
| Keywords: | Antigens, Tumor-Associated, Carbohydrate, Apoptosis, Caspases, Cell Line, Cell Line, Tumor, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, HL-60 Cells, Humans, Jurkat Cells, K562 Cells, Leukemia, Photochemotherapy, Photosensitizing Agents, Plant Lectins, Porphyrins, U937 Cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1394555 |
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