Abstract
Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.
Highlights
To the reason because low dose irradiation correlates with immune enhancement[4]
We showed that oncogene KRAS (Kirsten rat sarcoma viral oncogene homolog) induces reactive oxygen species (ROS) generation through activation of NADPH oxidase, which is a severe regulator for the KRAS induced cellular transformation[9,10]
When cell growth was investigated, we found that treatment of low dose irradiation did not block the cell proliferation in KRAS transformed MCF10A cells (Fig. 1B)
Summary
To the reason because low dose irradiation correlates with immune enhancement[4]. Low dose irradiation activated immune response ensues through the stimulation of both antigen-presenting cells and T lymphocytes, assisting intercellular reactions within the immunological synapse[5]. Underlying molecular mechanisms regarding the biological effect of low dose irradiation in human welfare remained largely obscure. We selected the breast cancer cell line to investigate the effect of low dose irradiation on malignant phenotype. Current therapies treating this cancer progression limit cancer development but still sustain the most common reason of cancer-related death among women worldwide[15]. We sought to develop a means by which efficiently KRAS induced malignant transformation could be suppressed using low dose irradiation so that simultaneously dosing with anticancer drug might provide the safe therapeutic effect that has so far remained obscure. Down-regulation of antioxidants confirms that these are key factor involved in low dose irradiation reduced malignant phenotype in transformed cells
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