Effects of fotemustine or dacarbasine on a melanoma cell line pretreated with therapeutic proton irradiation

Ristić-Fira, Aleksandra; Korićanac, Lela; Žakula, Jelena; Valastro, L.; Iannolo, Gioacchin; Privitera, Giuseppe; Cuttone, G.; Petrović, Ivana

doi:10.1186/1756-9966-28-50

Cited by 5 publications

(4 citation statements)

References 40 publications

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“…In ad di tion, apoptotic cell death was eval u ated 6, 12, 24 or 48 hours af ter treat ments with dexa meth a sone used as a pos i tive control, as well as with FM, DTIC, g-rays and pro tons. The best in duc tion of apoptosis in the HTB140 cells was achieved 48 hours af ter treat ment with drugs and/or pro tons [38,39].…”

Section: Discussionmentioning

confidence: 99%

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

Korićanac¹,

Zakula²,

Keta³

et al. 2013

NUCL TECH RAD PROT

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This study was conducted in order to evaluate the ability of carbon ions to induce DNA double-strand breaks and apoptosis in the radio-resistant human HTB140 melanoma cells. The cells were irradiated with 12C ions having the linear energy transfer of 258 keV/mm. Irradiations were performed in the dose range from 2 to 16 Gy. Induction of DNA double-strand breaks was evaluated 2 hour after irradiation through expression of gH2AX protein. Increased level of gH2AX detected in irradiated samples was especially high after irradiation with 12 and 16 Gy. Dose dependent increase of apoptosis was detected 48 hour after irradiation by flow-cytometry, with the maximum value of 20.4% after irradiation with 16 Gy, and the apoptotic index of 9.3. Pro-apoptotic effects of carbon ion beams were confirmed by changes of key molecules of the mitochondrial apoptotic pathway, p53 protein expression, Bax/Bcl-2 ratio and caspase-3 activation

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Section: Discussionmentioning

confidence: 99%

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

Korićanac¹,

Zakula²,

Keta³

et al. 2013

NUCL TECH RAD PROT

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“…Recently, new treatment options have been evaluated in the clinic and the results with immunotherapy and targeted therapy were promising [ 1 ]. Nevertheless, the initial excitement about the possibility of having discovered new effective approaches to treat melanoma has been followed by a degree of discouragement because these therapies are usually associated with high costs, side effects and none appears to be curative when used as a single agent [ 2 , 3 ]. Their efficacy may be enhanced in combination with other chemotherapeutic agents [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

New derivatives of the antimalarial drug Pyrimethamine in the control of melanoma tumor growth: an in vitro and in vivo study

Tommasino

Gambardella

Buoncervello

et al. 2016

J Exp Clin Cancer Res

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BackgroundThe antimalarial drug Pyrimethamine has been suggested to exert an antitumor activity by inducing apoptotic cell death in cancer cells, including metastatic melanoma cells. However, the dose of Pyrimethamine to be considered as an anticancer agent appears to be significantly higher than the maximum dose used as an antiprotozoal drug.MethodsHence, a series of Pyrimethamine analogs has been synthesized and screened for their apoptosis induction in two cultured metastatic melanoma cell lines. One of these analogs, the Methylbenzoprim, was further analyzed to evaluate cell-cycle and the mechanisms of cell death. The effects of Methylbenzoprim were also analyzed in a severe combined immunodeficiency (SCID)-mouse xenotransplantation model.ResultsLow dose of Methylbenzoprim was capable of inducing cytotoxic activity and a potent growth-inhibitory effect by arresting cell cycle in S-phase in melanoma cells. Methylbenzoprim was also detected as powerful antineoplastic agents in SCID-mouse although used at very low dose and as a single agent.ConclusionsOur screening approach led to the identification of a “low cost” newly synthesized drug (methylbenzoprim), which is able to act as an antineoplastic agent in vitro and in vivo, inhibiting melanoma tumor growth at very low concentrations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0409-9) contains supplementary material, which is available to authorized users.

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“…This time point was reported to be optimal for the evaluation of radiation effects on HTB140 cells24. Percentage of viable cells varied from 31.6 to 39 per cent and from 37.1 to 56.6 per cent compared to control for LET values of 197 and 382 keV/μm, respectively.…”

Section: Resultsmentioning

confidence: 98%

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 Journal of Medical Research

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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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Effects of fotemustine or dacarbasine on a melanoma cell line pretreated with therapeutic proton irradiation

Abstract: Background: Considering that HTB140 melanoma cells have shown a poor response to either protons or alkylating agents, the effects of a combined use of these agents have been analysed.

Cited by 5 publications

References 40 publications

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

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

New derivatives of the antimalarial drug Pyrimethamine in the control of melanoma tumor growth: an in vitro and in vivo study

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

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