Abstract
Purpose: Serotonin (5-HT) is implicated in the underlying mechanisms which mediate cell death following ionizing radiation exposure, however, effects appear to be cell type-dependent. We sought to further characterize the role of 5-HT and 5-HT receptors (5-HTRs) in the exacerbation of cell death following ionizing radiation exposure in human colon carcinoma cells.
Materials and methods: We examined the clonogenic survival of colon carcinoma HCT116 cells treated with 5-HT and the selective 5-HTR antagonists ketanserin (5-HT2A) and ondansetron (5-HT3), following exposure to direct ionizing radiation and irradiated cell-conditioned medium (ICCM). The relative expression of these target receptors was measured using western blotting.
Results: Western blotting results revealed that relative protein levels of the 5-HT2A and 5-HT3 receptors were similar. 5-HT concentration-dependent increases in cell death that occurred following direct ionizing radiation exposure were abolished by both 5-HTR antagonists. Death of nonirradiated cells recipient of ICCM was increased in a concentration-dependent manner by 5-HT when present during donor cell irradiation. Both 5-HTR antagonists completely abolished the increases in bystander-induced cell death generated by 5-HT. Finally, we show that exposure of cells to 5-HT prior to receipt of ICCM can also dictate the degree of bystander-induced cell death.
Conclusions: Our findings demonstrate a definitive role for 5-HT in the exacerbation of cell death following ionizing radiation exposure in colon carcinoma cells and highlight 5-HTRs as potential markers for predicting cellular radiosensitivity.
Acknowledgements
Thank you to the McMaster Honors Biology and Pharmacology Program for the support throughout the preparation of this work. Thank you to Sarah Cash for aiding with the preparation of figures.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
Notes on contributors
Jacob J. Curtis
Jacob J. Curtis, Hons BHSc (Pharmacology), is a former laboratory research assistant at the Department of Biology, McMaster University, Hamilton, ON, Canada and is currently pursuing a Doctor of Pharmacy at the Leslie Dan Faculty of Pharmacy at the University of Toronto, ON, Canada.
Nguyen T. K. Vo
Dr. Nguyen T. K. Vo, PhD, is a Postdoctoral Fellow at the Department of Biology, McMaster University, Hamilton, ON, Canada.
Colin B. Seymour
Dr. Colin B. Seymour, PhD, is a Professor at the Department of Biology, McMaster University, Hamilton, ON, Canada.
Carmel E. Mothersill
Dr. Carmel E. Mothersill, PhD, is Professor at the Department of Biology, McMaster University, Hamilton, ON, Canada.