Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

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.

Low dose radiation regulates BRAF-induced thyroid cellular dysfunction and transformation

“…We have previously shown that LDR have potential to reduce cancer progression at fractionated (1cGyx10) or single doses (0.1Gy or 10cGy) [17, 18]. In accordance, we confirmed that LDR diminishes the growth of 850-5C, BCPAP as well as N-thy ori-3-1 BRAF V600E transformed thyroid cancer cells at both doses (Additional file 1: Figure S1A).…”

“…The advance of interventional radiology has attracted growing interest in the biological effect of LDR below 0.1Gy doses [16]. From our previous studies, it has become apparent that the LDR has the potential to block KRAS-driven cellular transformation [17] and metastatic cancer progression in breast cancer cells [18]. As, most of the thyroid patients can be cured with surgical treatment together with radioactive iodide, however BRAF-mutated thyroid cancer cells have lower expression of sodium/iodide symporter ( NIS ), thyroid transcription factors ( TTF-1 and TTF-2 ), and thyroglobulin ( TG ) than those cells having wild-type (WT) BRAF [19], and are particularly refractory to radioiodine therapy [20].…”

Health Impacts of Low-Dose Ionizing Radiation: Current Scientific Debates and Regulatory Issues

“…This assumption has been confirmed by findings from animal studies which demonstrated that development of experimental tumors may be suppressed by low-dose radiation exposure by stimulation of the removal of preneoplastic cells and/or through prevention of metastasis of already existing cancer. 151 - 154 From these data, it is assumed that doses currently associated with routine diagnostic X-ray procedures (range from 1 to 100 mGy) fall in the “hormetic” zone for high-energy γ-ray photons 155 , 139 and therefore can likely be protective against cancer and several noncancer diseases.…”

Low-dose radiation decreases tumor progression via the inhibition of the JAK1/STAT3 signaling axis in breast cancer cell lines

“…In our previous work, we showed that LDR reduces the malignant phenotype in oncogene KRAS (Kirsten rat sarcoma viral oncogene homolog) transformed breast epithelial cells. This phenomenon is due to the LDR-induction of antioxidants counteracting KRAS-induced ROS levels in LDR-exposed cells 14 . As metastasis is associated with increased malignant tumor progression, we sought to examine the effects of LDR with regard to EMT in breast cancer cells.…”