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Research Paper
A chemotherapy-associated senescence bystander effect in breast cancer cells
Xu Di, Andrew Taylor Bright, Ricardo Bellott, Elizabeth Gaskins, Jacques Robert, Shawn Holt, David Gewirtz and Lynne Elmore
volume 7 | issue 6
June 2008Pages: 682 - 690
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A bystander effect typically refers to the death, altered growth, or damage of cells that have not directly received chemotherapy or irradiation. Cancer cells derived from solid tumors readily undergo senescence in response to chemotherapeutic agents, prompting us to test for the existence of a senescence bystander effect. MCF-7 breast cancer cells were acutely exposed to Adriamycin to trigger senescence. Naïve MCF-7 cells, when cultured in conditioned media from senescent breast cancer cells, growth arrested despite mitogenic stimulation and exhibited SA -β-galactosidase activity, an enlarged cell size, and stable upregulation of p21WAF1 protein, collectively indicating a senescent state. In contrast, HCT-116 colon cancer cells, which also undergo p53-mediated senescence in response to acute AdR, did not undergo growth inhibition or senescence when cultured with conditioned media from senescent HCT-116 cells. Reciprocal experiments indicated that naïve HCT-116 cells are susceptible to the growth inhibitory effects of a breast cancer-derived mediator, which is independent of residual drug in conditioned media. Our study reveals a novel action of Adriamycin, which may contribute to its potent anti-breast cancer activity and lead to the discovery of additional therapeutic targets for the exploitation of a senescence bystander effect.