Differential Impact of Cardioprotective Autophagy Modulation on Breast Cancer Therapy
Ling, Lauren A.
2023
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Doxorubicin is cardiotoxic and has been found to contribute to cardiovascular disease in breast cancer patients. The activation of autophagy, a cellular degradation pathway, has been found to be cardioprotective. However, the effects of autophagy modulation need to be further investigated to examine potential beneficial effects during breast cancer therapy. Thus, it was hypothesized that autophagy ... read moreactivation would have cardioprotective effects whilst affecting the cancer killing efficacy of doxorubicin on the MDA-MB-231-Luc and 4T1-Luc cell lines more significantly than the MCF7 cell line. Differential results in terms of autophagic flux, cell viability, and ROS accumulation were seen across cell lines. H9C2 and MDA-MB-231-Luc cell viability were both rescued by rapamycin when co-treated with doxorubicin, but not for the MCF7 and 4T1-Luc cells. Autophagy activation via starvation rescued viability for the 4T1-Luc and MDA-MB-231-Luc cell lines. Autophagic flux increased in the presence of doxorubicin in the MDA-MB-231-Luc cells, but decreased flux in the 4T1-Luc cells. All cell lines experienced significant ROS accumulation when starved, but not when treated with rapamycin. Autophagy activation generally appeared to have beneficial effects on the MDA-MB-231-Luc and H9C2 cell lines, but its impact was more differential on the other cell lines. Furthermore, autophagy activation via rapamycin and starvation led to differential effects across the cell lines. Thus, the hypothesis was found to be partially correct. Hence, more studies need to be conducted to investigate the reasoning behind the differential impacts of autophagy activation by method and to further classify cancer types and characteristics before any general conclusions can be drawn about the impact of autophagy modulation on doxorubicin treatment.
Thesis (B.S.)--Tufts University, 2023.
Submitted to the Dept. of Biology.
Committee: Lauren Crowe, Howard Chen.read less - ID:
- rj430k138
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