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

Stępnik, Maciej; Spryszyńska, Sylwia; Gorzkiewicz, Anna; Ferlińska, Magdalena

doi:10.17219/acem/60848

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…Collagen, a major extracellular matrix (ECM) component, is coated to scaffold to make cell adhere better and as a ligand of DDR1 (11). DDR1 functions as the unique receptor tyrosine kinase (RTK) which can be activated by collagen (12,13). PCL scaffolds were transferred into the 24-well plates and coated with collagen type I in different concentrations (10, 20, 40, 80, 160 and 320 µg/ml).…”

Section: Methodsmentioning

confidence: 99%

“…The acute T leukemia cell line Jurkat, Clone E6-1 (ATCC ® TIB-152™) was cultured in RPMI-1640 supplemented with 10% FBS and 1% penicillin/streptomycin. The cells were maintained at 37°C with 5% CO 2 and 95% air (13). For experiments on scaffolds, the seeding density is different from 2.5×10 5 to 5×10 5 cells/ml according to experiments and the seeding method was in strict accordance to the 3D Insert™ cell seeding protocol.…”

Section: Methodsmentioning

confidence: 99%

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3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

et al. 2019

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Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type I coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8−CD34−CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

et al. 2019

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“…For example, combining PJ34 with the histone deacetylase (HDAC) inhibitor vorinostat decreased cell proliferation [ 42 ]. By contrast, combination of PJ34 and the NOTCH inhibitor (N-[N[(3,5-difluorophenacetyl)-l-alanyl]- S -phenylglycine t -butyl ester) (DAPT), or PJ34 and doxorubicin, etoposide, cytarabine, or chlorambucil, did not enhance the cytotoxicity of either drug in Jurkat cells in vitro [ 43 , 49 ].…”

Section: Parp Inhibitors As a Potential Treatment For Haematological Malignanciesmentioning

confidence: 99%

“…When PJ34 was combined with the HDAC inhibitors, MS275 or vorinostat, these effects were potentiated [ 42 , 48 ]. By contrast, no potentiation was observed following combination with decitabine, doxorubicin, chlorambucil, cytarabine, or etoposide [ 42 , 49 ], suggesting that not all cytotoxic chemotherapeutics can be combined with PARPi to enhance their effects, and that careful consideration of any potential PARPi and chemotherapeutic combinations is required.…”

Section: Parp Inhibitors As a Potential Treatment For Haematological Malignanciesmentioning

confidence: 99%

PARP Inhibitors and Haematological Malignancies—Friend or Foe?

Skelding

Lincz

2021

Cancers

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Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite promising results in vitro, few clinical trials in humans for haematological malignancies have been performed, and additional investigation is required. Paradoxically, secondary haematological malignancies have arisen in patients after treatment with PARPi, raising concerns about their potential use as therapies for any blood or bone marrow-related disorders. Here, we provide a comprehensive review of the biological, pre-clinical, and clinical evidence for and against treating individual haematological malignancies with approved and experimental PARPi. We conclude that the promise of effective treatment still exists, but remains limited by the lack of investigation into useful biomarkers unique to these malignancies.

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“…Combining PJ34 with other anti-cancer treatments enabled reducing their cytotoxic doses and achieved efficient eradication of HL-60, Jurkat-T cells, multiple myeloma cellsPRMI8226/R and B16F10 melanoma cells [ 57 , 58 , 59 ].…”

Section: Pj34 Causes Eradication Of Human Cancer Cells In Xenografmentioning

confidence: 99%

The Modified Phenanthridine PJ34 Unveils an Exclusive Cell-Death Mechanism in Human Cancer Cells

Cohen-Armon

2020

Cancers

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This overview summarizes recent data disclosing the efficacy of the PARP inhibitor PJ34 in exclusive eradication of a variety of human cancer cells without impairing healthy proliferating cells. Its cytotoxic activity in cancer cells is attributed to the insertion of specific un-repairable anomalies in the structure of their mitotic spindle, leading to mitotic catastrophe cell death. This mechanism paves the way to a new concept of cancer therapy.

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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

Abstract: 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.

Cited by 8 publications

References 21 publications

3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression

PARP Inhibitors and Haematological Malignancies—Friend or Foe?

The Modified Phenanthridine PJ34 Unveils an Exclusive Cell-Death Mechanism in Human Cancer Cells

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