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Updated: Apr 19, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Photodynamic responsiveness of human leukemia Jurkat/A4 cells with multidrug resistant phenotype
A A Philchenkov1, E D Shishko1, M P Zavelevich1
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
Unlabelled:
Photodynamic therapy (PDT) is considered as a possible alternative approach to overcoming multidrug resistance (MDR). Analysis of cross-resistance to PDT in cells with different MDR pathways and resistance levels seems to be advantageous for elucidating the general mechanisms of cancer cell resistance to various treatment modalities.
Aim:
The aim of the study was to clarify whether the Jurkat/A4 leukemia cells with MDR phenotype are cross-resistant to PDT.
Methods:
Human T-cell acute lymphoblastic leukemia line Jurkat and Jurkat/A4 subline with MDR phenotype were used. 5-Aminolevulinic acid (ALA) and Photolon (a complex of chlorine-e6 and polyvinylpyrrolidone; PL) or gold nanocomposite of PL were applied as photosensitizers. The cells were pretreated with photosensitizers and exposed to laser radiation at corresponding wavelengths. The phototoxicity was assessed in trypan blue exclusion test. The hypodiploid cell fraction was analyzed by flow cytometry of propidium iodide-stained cells. Expression of genes related to PDT resistance was analyzed by microarray technique with Affymetrix U133A chips.
Results:
ALA-mediated PDT resulted in dose-dependent cell death in both lines, the relative photodynamic efficacy in Jurkat/A4 cells being inferior to that in the parental Jurkat cells. There was no correlation between phototoxicity and apoptosis induction both in Jurkat and Jurkat/A4 cells. PL-mediated general phototoxicity in Jurkat cells amounted up to 75% at the maximal photosensitizer dose with about 40% of apoptotic death fraction. PL-phototoxicity in Jurkat/A4 cells was considerably lower. In contrast to Jurkat cells, PL-gold composite did not increase the efficacy of photosensitization as compared to free PL in Jurkat/A4 cells.
Conclusions:
Multidrug-resistant Jurkat/A4 cells exhibit reduced sensitivity to phototoxic effect in comparison with parental Jurkat cells independently of nature of the photosensitizer being assayed.
Insights
Multidrug-resistant (MDR) leukemia cells show reduced sensitivity to photodynamic therapy (PDT), an approach explored to overcome cancer resistance. This study investigated cross-resistance to PDT in Jurkat/A4 cells, finding they were less affected by treatment.
Area of Science:
- Oncology
- Biochemistry
- Photomedicine
Background:
- Photodynamic therapy (PDT) is a promising strategy to overcome multidrug resistance (MDR) in cancer.
- Understanding cross-resistance mechanisms in MDR cells is crucial for developing effective cancer treatments.
Purpose of the Study:
- To determine if Jurkat/A4 leukemia cells with MDR phenotype exhibit cross-resistance to photodynamic therapy (PDT).
Main Methods:
- Jurkat and Jurkat/A4 leukemia cell lines were treated with photosensitizers (5-aminolevulinic acid or Photolon) followed by laser irradiation.
- Phototoxicity was assessed using trypan blue exclusion and apoptosis assays.
- Gene expression related to PDT resistance was analyzed via microarray.
Main Results:
- MDR Jurkat/A4 cells demonstrated reduced photodynamic efficacy compared to parental Jurkat cells, irrespective of the photosensitizer used.
- No correlation was found between phototoxicity and apoptosis induction in either cell line.
- A gold nanocomposite of Photolon did not enhance photosensitization efficacy in MDR cells.
Conclusions:
- Multidrug-resistant Jurkat/A4 cells are less sensitive to PDT compared to their drug-sensitive counterparts.
- This reduced sensitivity is independent of the photosensitizer employed, suggesting a general resistance mechanism.
- PDT may face challenges in treating cancers with established MDR phenotypes.
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