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Eribulin Mesylate Improves Cisplatin-Induced Cytotoxicity of Triple-Negative Breast Cancer by Extracellular
Hyemi Ko1,2, Myungsun Lee2, Eunyoung Cha2
1Department of Surgery, Chungnam National University Hospital, Jung-gu, Daejeon 35015, Korea.
Abstract:
Background and Objectives; Triple-negative breast cancer (TNBC) is associated with poor patient prognosis because of its multiple molecular features. Thus, more effective treatment for TNBC is urgently needed. This study determined the possible involvement of ERK1/2 activation in cisplatin-induced cytotoxicity in TNBC by providing additional eribulin treatment. Materials and Methods; We investigated cell viability and apoptosis caused by eribulin, cisplatin, or co-treatment in HCC38, MDA-MB-231, and SKBR3 human breast cancer cells. Results; Cisplatin significantly lowered cell viability and caused high apoptotic cell death in all breast cancer cell lines. The viability of TNBC cells was significantly lower in the group co-treated with cisplatin and eribulin than in the cisplatin-only treatment group. Additional eribulin treatment significantly enhanced PARP cleavage and caspase-3 activity in cisplatin-treated TNBC cells. Moreover, cisplatin treatment activated ERK1/2 in all breast cancer cell lines. The cisplatin and eribulin combination synergistically activated ERK1/2 in TNBC cells compared with the cisplatin-only treatment. Administration of the ERK1/2 inhibitor PD98059 increased the viability of TNBC cells treated with cisplatin plus eribulin. Conclusions; Eribulin could synergize the cytotoxic and apoptotic activities of cisplatin and increase ERK1/2 activation, thus enhancing anti-cancer effects against TNBC cells.
Insights
Eribulin combined with cisplatin enhances anti-cancer effects against triple-negative breast cancer (TNBC) by increasing cell death and activating ERK1/2 signaling. This combination therapy offers a promising strategy for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic options.
- There is an urgent need for novel and effective treatment strategies to improve patient outcomes in TNBC.
Purpose of the Study:
- To investigate the synergistic effects of eribulin and cisplatin on triple-negative breast cancer (TNBC) cells.
- To determine the role of ERK1/2 activation in the combined cytotoxic and apoptotic response induced by eribulin and cisplatin in TNBC.
Main Methods:
- Assessed cell viability and apoptosis in human breast cancer cell lines (HCC38, MDA-MB-231, SKBR3) treated with eribulin, cisplatin, or their combination.
- Quantified PARP cleavage and caspase-3 activity to evaluate apoptosis induction.
- Measured ERK1/2 activation and assessed the impact of the ERK1/2 inhibitor PD98059 on cell viability.
Main Results:
- Cisplatin significantly reduced cell viability and induced apoptosis across all tested breast cancer cell lines.
- The combination of eribulin and cisplatin demonstrated significantly lower TNBC cell viability and enhanced apoptosis compared to cisplatin alone.
- Combined treatment synergistically activated ERK1/2 signaling in TNBC cells, and inhibiting ERK1/2 partially reversed the enhanced cytotoxicity.
Conclusions:
- Eribulin potentiates the cytotoxic and apoptotic effects of cisplatin in triple-negative breast cancer (TNBC).
- The synergistic anti-cancer activity of the eribulin-cisplatin combination is associated with increased ERK1/2 activation.
- This combination therapy represents a promising approach for enhancing treatment efficacy against TNBC.
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