Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker 3.8)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 3, May-June, p. 379–385

doi: 10.17219/acem/60848

Publication type: original article

Language: English

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Cytotoxicity of anticancer drugs and PJ-34 (poly(ADP-ribose)polymerase-1 (PARP-1) inhibitor) on HL-60 and Jurkat cells

Maciej Stępnik1,A,F, Sylwia Spryszyńska1,B,C, Anna Gorzkiewicz1,B,C, Magdalena Ferlińska1,B,C

1 Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

Abstract

Background. The majority of the clinical trials with poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors were conducted or are ongoing in patients with solid tumors, while trials with leukemia patients are less frequent. Surprisingly scarce data is available on the combinatory effects of PARP inhibitors with DNA damaging antitumor drugs in leukemic cells (primary cells or established lines).
Objectives. The aim of the present study was to assess the effect of PJ-34 (PARP-1 inhibitor) on the cytotoxicity of different antileukemic drugs with different DNA damaging mechanisms and potency (doxorubicin, etoposide, cytarabine and chlorambucil) in human leukemic Jurkat and HL-60 cells.
Material and Methods. Different exposure scenarios were applied: 1) 72 h simultaneous incubation with PJ-34 (2.5 or 5 μM for Jurkat and HL-60 cells, respectively) and a drug used at a wide concentration range; 2) preincubation of the cells with PJ-34 for 24 h and then with a combination of PJ-34 + drug for an additional 48 h; 3) preincubation of the cells with the drug for 24 h with a subsequent incubation with a combination of PJ-34 + drug for an additional 48 h. Cytotoxicity was assessed using a WST-1 reduction test.
Results. It was determined that PJ-34, when used in all 3 scenarios, did not induce any significant enhancement of cytotoxicity of the drugs either in Jurkat or in HL-60 cells.
Conclusion. Although the results do not confirm the beneficial effects of PARP inhibition in combination treatment of the leukemic cells, we propose that future studies including an additional step with the inhibition of DNA repair by homologous recombination should provide promising results.

Key words

PJ-34, doxorubicin, cytarabine, chlorambucil, etoposide

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