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Cited by 57Telomeres, Telomerase, and SenescenceCell death mechanisms and regulationCancer-related Molecular Pathways

A chemotherapy-associated senescence bystander effect in breast cancer cells

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Di, Xu, Bright, Andrew Taylor, Bellott, Ricardo, Gaskins, Elizabeth, Robert, Jacques, Holt, Shawn, Gewirtz, David A., Elmore, Lynne·2008·Cancer Biology & Therapy
DOI 10.4161/cbt.7.6.5861
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Abstract

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-beta-galactosidase activity, an enlarged cell size and stable upregulation of p21(WAF1) 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, like MCF-7 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.

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  • Senescent cells are able to promote senescence of adjacent cells through both the SASP and direct cell-cell interactions, thus also limiting the propagation of not yet senescent premalignant or fully malignant cells in their vicinity.

    “Indeed, senescent cells are able to promote senescence of adjacent cells through both the SASP and direct cell-cell interactions, thus also limiting the propagation of not yet senescent premalignant or fully malignant cells in their vicinity 63,84,137-139 .”

    From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [139]

    The Discussion (page unavailable) reports that a soluble factor from chemotherapy-senescent MCF-7 breast cancer cells induced senescence in naïve breast cancer cells, supporting the bystander-effect portion of the claim. The paper does not establish direct cell-cell interactions as a mechanism or show this effect in premalignant cells; its findings are narrower than the citing sentence. (LLM, conf=0.88)

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Cited by

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Authors
Di, X., Bright, A. T., Bellott, R., Gaskins, E., Robert, J., Holt, S., Gewirtz, D. A., & Elmore, L.
Affiliations
  • Virginia Commonwealth University (US)
  • Institut Bergonié (FR)
ORCID
Venue
Cancer Biology & Therapy
Publisher
Informa UK Limited
Published
2008-06
Volume
7
Issue
6
Pages
864-872
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
DOI
10.4161/cbt.7.6.5861
OpenAlex
W2064526080
Cited by
57
References
0
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 4
FWCI
2.04
Type
journal article
Language
en
Open access
Locations
  • Cancer Biology & Therapy (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense (W81XWH, W81XWH-05-1)
  • Virginia Commonwealth University
  • National Institutes of Health (06-01, W81XWH)
  • National Cancer Institute (K01CA105050)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
chemotherapy-induced senescence, breast cancer, doxorubicin, conditioned medium, p21, SA-β-galactosidase, MCF-7 cells, HCT116 cells, growth arrest, senescence-associated secretory phenotype
MeSH terms
Antineoplastic Agents, Breast Neoplasms, Chromatography, High Pressure Liquid, Doxorubicin, Drug Screening Assays, Antitumor, Humans, Models, Biological, Tumor Suppressor Protein p53, Cellular Senescence, Bystander Effect, HCT116 Cells, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21

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