Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin

• DOI: 10.1371/journal.pone.0135356
• Publication Date: 2015-08-17T17:38:41Z
• Authors: Quinn Matthews; Martin Isabelle; Samantha J. Harder; Julian Smazynski; Wayne Beckham; Alexandre G. Brolo; Andrew Jirasek; Julian J. Lum
• Keywords: Radioresistance; Radiosensitivity

Altered cellular metabolism is a hallmark of tumor cells and contributes to host properties associated with resistance radiotherapy. Detection radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses radiation, we performed label-free single cell Raman spectroscopy on series human cancer lines detected accumulation intracellular glycogen. The increase in glycogen post-irradiation was highest lung (H460) breast (MCF7) compared prostate (LNCaP) cells. In response the appearance this signature correlated radiation resistance. Moreover, buildup linked phosphorylation GSK-3β, canonical modulator survival following exposure key regulator metabolism. When MCF7 were irradiated presence anti-diabetic drug metformin, there significant decrease amount suppression by metformin increased radiosensitivity. contrast cells, had minimal effects both level H460 Our data demonstrate novel approach spectral monitoring assess levels potential marker mechanism therapy.