Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death

Cell Death Dis. 2018 Jun 18;9(7):716. doi: 10.1038/s41419-018-0747-y.

Abstract

Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Bystander Effect* / drug effects
  • Bystander Effect* / radiation effects
  • Cell Death / drug effects
  • Cell Death / radiation effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Gamma Rays* / therapeutic use
  • HCT116 Cells
  • Humans
  • Jurkat Cells
  • MCF-7 Cells
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / radiotherapy
  • Oxaliplatin / pharmacology
  • Paclitaxel / pharmacology
  • Radiotherapy

Substances

  • Antineoplastic Agents
  • Oxaliplatin
  • Paclitaxel
  • Cisplatin