Carbon ions induce DNA double strand breaks and apoptosis in HTB140 melanoma cells

Korićanac, Lela; Zakula, Jelena; Keta, Otilija; Cirrone, G.A.P.; Cuttone, G.; Ristić-Fira, Aleksandra; Petrović, Ivan

doi:10.2298/ntrp1302195k

Cited by 2 publications

(2 citation statements)

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“…The longer G2 arrest may be attributed to the higher level of unrepaired DNA damages. These findings are in agreement with our previous results signifying induction of DSBs in HTB140 cells after exposure to 12 C ions18.…”

Section: Discussionsupporting

confidence: 94%

“…Western blot analysis : For the Western blot analysis cells were collected, washed with PBS, lysed in a cell lysis buffer and samples were prepared as previously described18. The membranes were incubated with primary antibodies against p53, Bcl-2, Bax, NFκB and PARP (poly ADP ribose polymerase) (Cell Signaling, Danvers, MA, USA) (1:1000 dilution) at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

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Carbon ions of different linear energy transfer (LET) values induce apoptosis & G2 cell cycle arrest in radio-resistant melanoma cells

Zakula¹,

Lela²,

Otilija³

et al. 2016

Indian J Med Res

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Background & objectives:The main goal when treating malignancies with radiation is to deprive tumour cells of their reproductive potential. One approach is to induce tumour cell apoptosis. This study was conducted to evaluate the ability of carbon ions (12C) to induce apoptosis and cell cycle arrest in human HTB140 melanoma cells.Methods:In this in vitro study, human melanoma HTB140 cells were irradiated with the 62 MeV/n carbon (12C) ion beam, having two different linear energy transfer (LET) values: 197 and 382 keV/μm. The dose range was 2 to 16 Gy. Cell viability was estimated by the sulforhodamine B assay seven days after irradiation. The cell cycle and apoptosis were evaluated 48 h after irradiation using flow cytometry. At the same time point, protein and gene expression of apoptotic regulators were estimated using the Western blot and q-PCR methods, respectively.Results:Cell viability experiments indicated strong anti-tumour effects of 12C ions. The analysis of cell cycle showed that 12C ions blocked HTB140 cells in G2 phase and induced the dose dependent increase of apoptosis. The maximum value of 21.8 per cent was attained after irradiation with LET of 197 keV/μm at the dose level of 16 Gy. Pro-apoptotic effects of 12C ions were confirmed by changes of key apoptotic molecules: the p53, Bax, Bcl-2, poly ADP ribose polymerase (PARP) as well as nuclear factor kappa B (NFκB). At the level of protein expression, the results indicated significant increases of p53, NFκB and Bax/Bcl-2 ratio and PARP cleavage. The Bax/Bcl-2 mRNA ratio was also increased, while no change was detected in the level of NFκB mRNA.Interpretation & conclusions:The present results indicated that anti-tumour effects of 12C ions in human melanoma HTB140 cells were accomplished through induction of the mitochondrial apoptotic pathway as well as G2 arrest.

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Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Carbon ions of different linear energy transfer (LET) values induce apoptosis & G2 cell cycle arrest in radio-resistant melanoma cells

Zakula¹,

Lela²,

Otilija³

et al. 2016

Indian J Med Res

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A Monte Carlo study for the calculation of the average linear energy transfer (LET) distributions for a clinical proton beam line and a radiobiological carbon ion beam line

Romano¹,

Cirrone²,

Cuttone³

et al. 2014

Phys. Med. Biol.

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Fluence, depth absorbed dose and linear energy transfer (LET) distributions of proton and carbon ion beams have been investigated using the Monte Carlo code Geant4 (GEometry ANd Tracking). An open source application was developed with the aim to simulate two typical transport beam lines, one used for ocular therapy and cell irradiations with protons and the other for cell irradiations with carbon ions. This tool allows evaluation of the primary and total dose averaged LET and predict their spatial distribution in voxelized or sliced geometries. In order to reproduce the LET distributions in a realistic way, and also the secondary particles' contributions due to nuclear interactions were considered in the computations. Pristine and spread-out Bragg peaks were taken into account both for proton and carbon ion beams, with the maximum energy of 62 MeV/n. Depth dose distributions were compared with experimental data, showing good agreement. Primary and total LET distributions were analysed in order to study the influence of contributions of secondary particles in regions at different depths. A non-negligible influence of high-LET components was found in the entrance channel for proton beams, determining the total dose averaged LET by the factor 3 higher than the primary one. A completely different situation was obtained for carbon ions. In this case, secondary particles mainly contributed in the tail that is after the peak. The results showed how the weight of light and heavy secondary ions can considerably influence the computation of LET depth distributions. This has an important role in the interpretation of results coming from radiobiological experiments and, therefore, in hadron treatment planning procedures.

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Carbon ions induce DNA double strand breaks and apoptosis in HTB140 melanoma cells

Cited by 2 publications

References 43 publications

Carbon ions of different linear energy transfer (LET) values induce apoptosis & G2 cell cycle arrest in radio-resistant melanoma cells

Carbon ions of different linear energy transfer (LET) values induce apoptosis & G2 cell cycle arrest in radio-resistant melanoma cells

A Monte Carlo study for the calculation of the average linear energy transfer (LET) distributions for a clinical proton beam line and a radiobiological carbon ion beam line

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