Sara Pignatta1, Michela Cortesi2, Chiara Arienti2, Michele Zanoni2, Claudia Cocchi2, Anna Sarnelli3, Donatella Arpa4, Filippo Piccinini5, Anna Tesei6. 1. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy. Electronic address: sara.pignatta@irst.emr.it. 2. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy. 3. Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 4. Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Scientific Directorate, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy. Electronic address: anna.tesei@irst.emr.it.
Abstract
BACKGROUND: Since its discovery in the late 19th century, radiotherapy has been one of the most important medical treatments in oncology. Recently, fasting or short-term starvation (STS) in cancer patients undergoing chemotherapy has been studied to determine its potential for enhancing the therapeutic index and for preventing side- effects, but no data are available in the radiotherapy setting. We thus decided to investigate the effects in vitro of STS in combination with radiotherapy in metastatic cancer cells and non-cancer cells. METHODS: Cells were incubated in short-term starvation medium (STS medium, 0·5 g/L glucose + 1% FBS) or in control medium (CM medium, 1 g/L glucose + 10 % FBS) for 24 h and then treated with single high-dose radiation. A plexiglass custom-built phantom was used to irradiate cells. DNA damage was evaluated using alkaline comet assay and theCometAnalyser software. The cell surviving fraction was assessed by clonogenic assay. FINDING: STS followed by single high-dose radiation significantly increased DNA damage in metastatic cancer cell lines but not in normal cells. Furthermore, STS reduced the surviving fraction of irradiated tumor cells, indicating a good radio-sensitizing effect on metastatic cell lines. This effect was not observed in non-tumor cells. INTERPRETATION: Our results suggest that STS may alter cellular processes, enhancing the efficacy of radiotherapy in metastatic cancer cellsin vitro. Interestingly, STS has radioprotective effect on the survival of healthy cells.
BACKGROUND: Since its discovery in the late 19th century, radiotherapy has been one of the most important medical treatments in oncology. Recently, fasting or short-term starvation (STS) in cancerpatients undergoing chemotherapy has been studied to determine its potential for enhancing the therapeutic index and for preventing side- effects, but no data are available in the radiotherapy setting. We thus decided to investigate the effects in vitro of STS in combination with radiotherapy in metastatic cancer cells and non-cancer cells. METHODS: Cells were incubated in short-term starvation medium (STS medium, 0·5 g/L glucose + 1% FBS) or in control medium (CM medium, 1 g/L glucose + 10 % FBS) for 24 h and then treated with single high-dose radiation. A plexiglass custom-built phantom was used to irradiate cells. DNA damage was evaluated using alkaline comet assay and theCometAnalyser software. The cell surviving fraction was assessed by clonogenic assay. FINDING: STS followed by single high-dose radiation significantly increased DNA damage in metastatic cancer cell lines but not in normal cells. Furthermore, STS reduced the surviving fraction of irradiated tumor cells, indicating a good radio-sensitizing effect on metastatic cell lines. This effect was not observed in non-tumor cells. INTERPRETATION: Our results suggest that STS may alter cellular processes, enhancing the efficacy of radiotherapy in metastatic cancer cellsin vitro. Interestingly, STS has radioprotective effect on the survival of healthy cells.
Authors: Anna Tesei; Francesco Di Virgilio; Michele Zanoni; Alba Clara Sarti; Alice Zamagni; Michela Cortesi; Sara Pignatta; Chiara Arienti; Michela Tebaldi; Anna Sarnelli; Antonino Romeo; Daniela Bartolini; Luigino Tosatto; Elena Adinolfi Journal: Cell Death Dis Date: 2022-01-24 Impact factor: 9.685