In vitro radiosensitization by eribulin in human cancer cell lines

Benlloch, Raquel; Castejón, Raquel; Rosado, Silvia; Coronado, María José; Sánchez, Patricia Mills; Romero, Jesús

doi:10.5603/rpor.a2022.0049

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…Furthermore, while our results suggest that olaparib enhanced eribulin-induced cell cycle arrest in all cells, there is a heterogeneous response to the combination of both drugs on apoptosis. This agrees with the reported effect of eribulin on cell cycle progression and heterogenous induction of programmed cell death [39,40].…”

Section: )supporting

confidence: 93%

PARP Inhibition Sensitizes Breast Cancer Cells to Eribulin

Sharif-Askari¹,

Panasci²,

Aloyz³

2023

Front. Biosci. (Landmark Ed)

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Background: Poly(ADP-ribose) polymerases 1 and 2 (PARP1, 2), and 3 mediate protein modifications that facilitate the recruitment of DNA repair factors to single and double strand breaks. PARP3 is unique in that it is also required for efficient mitotic progression and stabilization of the mitotic spindle. Eribulin, an anti-microtubule agent used clinically to treat breast cancer, exerts its cytotoxicity by altering microtubule dynamics resulting in cell cycle arrest and apoptosis. Herein, we hypothesize that the pan PARP inhibitor olaparib has the potential to enhance the cytotoxicity of eribulin by halting mitosis through inhibition of PARP3. Methods: The effect of olaparib on eribulin cytotoxicity was assessed using the Sulforhodamine (SRB) assay, with two triple negative breast cancer cell lines and an estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer cell line. Alteration by the treatments on PARP3 activity and microtubule dynamics were assessed utilizing a chemiluminescent enzymatic assay and immunofluorescence, respectively. The effect of the treatments on cell cycle progression and apoptosis induction were assessed by flow cytometry using propidium iodide and Annexin V staining, respectively. Results: Our results demonstrate that non-cytotoxic concentrations of olaparib sensitize breast cancer cells regardless of ER status. Mechanistically, our results indicate that olaparib potentiates eribulin-induced cell cycle arrest at the G2/M boundary, PARP3 inhibition and microtubule destabilizing resulting in mitotic catastrophe and apoptosis. Conclusions: In breast cancer (regardless of ER status) settings, treatment outcomes could be improved by the incorporation of olaparib in eribulin treatment regimens.

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Section: )supporting

confidence: 93%

PARP Inhibition Sensitizes Breast Cancer Cells to Eribulin

Sharif-Askari¹,

Panasci²,

Aloyz³

2023

Front. Biosci. (Landmark Ed)

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“…They reported that apoptotic cells even after 6 Gy radiation were not increased significantly. [ 28 ]…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Relationship between Intrinsic Radiosensitivity (Survival Fraction at 2 Gy) and Gamma-H2AX Test and Apoptosis of Lymphocytes in Breast Cancer Patients

Bahreyni Toosi,

Azimian,

Salek

et al. 2024

Journal of Medical Signals &Amp; Sensors

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Background: Radiotherapy is one of the routine treatment strategies for breast cancer (BC) patients. Different responses of the patient to radiation due to different intrinsic radiosensitivity (RS) were induced to the researcher try to introduce a standard assay for the prediction of RS. Clonogenic assay is recognized as a gold standard method in this subject but because of some of its disadvantages, it is needed for alternative assays. In this study, two assays were evaluated for this reason in ten BC patients with different RSs. Methods: The peripheral blood of 10 volunteers with BC was obtained, and the peripheral blood mononuclear cells were extracted. After exposed with 2 Gy, survival fraction at 2 Gy (SF2) was calculated by clonogenic assay. γ-H2AX assay was performed for all patients, and apoptosis assay was evaluated for three represented categorized patients. Results: RS of patients showed SF2 and categorized in three groups (high, medium, and low RS). Double-strand breaks (DSBs) were decreased in high radiosensitive patients, but the residual DSBs were clearly higher than other two groups. It is shown that the repair system in these patients is lower active than others. Apoptosis frequency in patient 4 is highly active which could induce the enhancement of her RS. Conclusion: γ-H2AX and apoptosis assays could predict the intrinsic RS, but evaluation of them separately is not sufficient for this aim. It is necessary to consider all the parameters together and consideration of the combination of assays could fit a better prediction of intrinsic RS.

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In vitro radiosensitization by eribulin in human cancer cell lines

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited.

Cited by 2 publications

References 25 publications

PARP Inhibition Sensitizes Breast Cancer Cells to Eribulin

PARP Inhibition Sensitizes Breast Cancer Cells to Eribulin

Evaluation of Relationship between Intrinsic Radiosensitivity (Survival Fraction at 2 Gy) and Gamma-H2AX Test and Apoptosis of Lymphocytes in Breast Cancer Patients

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