Proton therapy is used today to treat many cancers and is particularly appropriate in situations where surgery options are limited, and conventional radiotherapy presents unacceptable risks to patients. A few years ago, it was suggested that an increase of up to a factor of two of the doses at the proton Bragg peak could be achieved if boron is accumulated in the tumor tissues. The mechanism responsible for a higher dose was suggested to be related to proton-boron fusion reactions, leading to the production of high Linear Energy Transfer (LET) α-particles. Nowadays there are single works showing the effectiveness of proton beam irradiation boron-11-containing cancer cells. A limited number of the studies devoted to the application of 11B(p,3a) nuclear reaction in proton therapy and lack of consistency in their results do not allow to judge about the prospects of the boron-containing drugs utilization in proton therapy to increase its antitumor efficacy. In this work, we experimentally test the possibility to enhance proton biological effectiveness in boron-11-containing cancer cells in vitro. Human glioblastoma cells were preincubated with boron compound (Na2B4O7, sodium tetraborate) and irradiated with increasing doses 2-8 Gy at the proton Bragg peak. To test whether the physical nuclear reaction 11B(p,3a) results in an enhancement of the cancer cell death by high-energy proton beam irradiation, cell lines were also irradiated with graded doses 2-8 Gy using γ-ray source. The ability of boron compound to activate the cancer cell death with protons at the Bragg peak irradiation was shown in vitro. At the same time, weaker similar effect was determined for gamma-irradiation that may indicate not only the physical nature of influence boron at irradiated cancer cell viability but a specific biological effect. The data suggest that the combined effect of proton therapy with 11 B on glioma cells increases their sensitivity to proton irradiation with low toxicity of the boron compound for cells of normal morphology.

Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.

Targeting sonic hedgehog pathway in combination with proton radiation or gamma irradiation decreases viability of glioma cell lines .

The pro-apoptotic effect of new 2-thioxo-4-thiazolidinone derivative Les-3331 on MCF-7 and MDA-MB-231 cell lines ..