Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points.
Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549). Proton beam (3MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton-irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44(+), a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion.
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India. Electronic address: narangh@barc.gov.in.
Himanshi
H
Narang
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Amit
A
Kumar
Radiological Physics and Advisory Division.
Nagesh
N
Bhat
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Badri N
BN
Pandey
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Anu
A
Ghosh
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects*; D016923:Cell Death / Q000235:genetics / Q000528:radiation effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000528:radiation effects*; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011522:Protons
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D011522:Protons
Cancer stem cell; Cell cycle; Epithelial-mesenchymal transition; Gene expression; Proton beam; Radiation