Radiosensitizing effects of trabectedin on human A549 lung cancer cells and HT-29 colon cancer cells

Manda, Katrin; Präkelt, Tina; Schröder, Tonja; Kriesen, Stephan; Hildebrandt, Guido

doi:10.1007/s10637-019-00852-x

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Irradiation was administered at room temperature using a linear accelerator ONCOR Expression (Siemens, Erlangen, Germany) at 3.75 Gy/min (energy 6 MeV) as described before [24]. The irradiation doses used were 0 Gy, 2 Gy, 4 Gy, 6 Gy, and 8 Gy.…”

Section: Irradiationmentioning

confidence: 99%

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

2020

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Sodium selenite is often given to moderate the side effects of cancer therapy to enhance the cellular defence of non-cancerous cells. To determine whether sodium selenite during radiotherapy protects not only normal cells but also cancer cells, which would imply a reduction of the desired effect of irradiation on tumour during radiotherapy, the effect of the combined treatment of irradiation and sodium selenite was investigated. Human bronchial cells from carcinoma (A549) and normal tissue (BEAS-2B) were treated with sodium selenite and effects on growth and in combination with radiation on metabolic activity and cell cycle distribution were studied. The influence on radiosensitivity was determined via colony forming assays using different solvents of sodium selenite and treatment schedules. It was shown that sodium selenite inhibits growth and influences cell cycle distribution of both normal and tumour cells. Metabolic activity of normal cells decreased more rapidly compared to that of cancer cells. The influence of sodium selenite on radiation response depended on the different treatment schedules and was strongly affected by the solvent of the agent. It could be shown that the effect of sodium selenite on radiation response is strongly dependent on the respective experimental in vitro conditions and ranges from lead to an initially suspected but ultimately no real radioprotection to radiosensitizing up to no effect in one and the same cell line. This might be a reason for controversially described cell responses to radiation under the influence of sodium selenite in studies so far.

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Section: Irradiationmentioning

confidence: 99%

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

2020

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“…Several mechanisms of action have been described for this drug such as the interference with DNA transcription (as a consequence of its binding to the minor groove of DNA), its ability to induce cell cycle arrest [9], and its effects on tumoral microenvironment, targeting macrophages [10]. Preclinical data showed that trabectedin had a radiosensitizing effect on several cell lines [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center

Hindi

García

Sánchez-Camacho

et al. 2020

Cancers

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Symptomatic control and tumoral shrinkage is an unmet need in advanced soft-tissue sarcoma (STS) patients beyond first-line. The combination of trabectedin and radiotherapy showed activity in a recently reported clinical trial in this setting. This retrospective series aims to analyze our experience with the same regimen in the real-life setting. We retrospectively reviewed advanced sarcoma patients treated with trabectedin concomitantly with radiotherapy with palliative intent. Growth-modulation index (GMI) was calculated as a surrogate of efficacy. Forty metastatic patients were analyzed. According to RECIST, there was one (2.5%) complete response, 12 (30%) partial responses, 18 (45%) disease stabilizations, and nine (22.5%) progressions. After a median follow-up of 15 months (range 2–38), median progression-free survival (PFS) and overall survival (OS) were 7.5 months (95% CI 2.8–12.2) and 23.5 months (95% CI 1.1–45.8), respectively. Median GMI was 1.42 (range 0.19–23.76), and in 16 (53%) patients, it was >1.33. In patients with GMI >1.33, median OS was significantly longer than in those with GMI 0–1.33 (median OS 52.1 months (95% CI not reached) vs. 8.9 months (95% CI 6.3–11.6), p = 0.028). The combination of trabectedin plus radiotherapy is an active therapeutic option in patients with advanced STS, especially when tumor shrinkage for symptomatic relief is needed.

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“…Both examined cell lines in our study are characterized by a mutation in the p53 tumor suppressor (FaDu: p.R248L; T98G: p.M237I) [ 23 ]. The two cell lines, SK-MEL-28 as well as HT-29, in which piperine was also shown to have an effect [ 17 , 22 ], are also p53-mutated (SK-MEL-28: p.L145R; HT-29: p.R273H) [ 24 ]. However, it cannot be generally concluded from this that the combined effect of piperine and radiation is only present in p53-mutated cells or that there is no effect in wild-type cells.…”

Section: Discussionmentioning

confidence: 99%

“…The maximum of DNA double-strand breaks can be seen about 30–90 min after the damage event, which is why the first fixation point in this work was chosen after 0.5 h. The 24 h point in time was also examined, since the repair of radiation-induced DNA-DSB is then completed and conclusions can be drawn about the repair capacity. The detached slides were then fixed and stained in accordance with the protocol already described [ 24 ]. The foci of a total of 50 cell nuclei were counted for each experiment using the fluorescence microscope.…”

Section: Methodsmentioning

confidence: 99%

Pepper Alkaloid Piperine Increases Radiation Sensitivity of Cancer Cells from Glioblastoma and Hypopharynx In Vitro

Diehl

Hildebrandt

Manda

2022

IJMS

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In our study, our aim was to examine the cytotoxic and radio-sensitizing effect of the alkaloid piperine, a major pungent of black pepper, on two different human epithelial tumor cell lines in vitro. The growth of the human cell lines T98G (glioblastoma) and FaDu (hypopharyngeal carcinoma) was examined under the influence of piperine in different concentrations. In addition, after combined treatment with ionizing radiation, long-term survival was investigated with a colony formation assay. The proliferation was analyzed using the BrdU-assay, while the DNA repair capacity was examined via the γH2AX assay. Piperine reduced the growth of both cell lines in a concentration-dependent manner as well as a time-dependent one. After combined treatment with piperine and ionizing radiation, an inhibition of clonogenic survival could be proven. A reduced proliferation capacity and an additive effect on DNA damage 24 h after irradiation are possible causal mechanisms, which were also demonstrated for both cell lines. Based on the results presented in this study, piperine was shown to have cytotoxic antitumor activity and a radio-sensitizing effect in micromolar concentrations in the human tumor cells that were tested. Based on these results piperine represents a potential therapeutic option in radio-oncological treatment.

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Radiosensitizing effects of trabectedin on human A549 lung cancer cells and HT-29 colon cancer cells

Cited by 7 publications

References 38 publications

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center

Pepper Alkaloid Piperine Increases Radiation Sensitivity of Cancer Cells from Glioblastoma and Hypopharynx In Vitro

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