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Optimization of cytotoxic activity of Nocardia sp culture broths using a design of experiments.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-01-14 , DOI: 10.1371/journal.pone.0227816
Alba Noël 1 , Gwendoline Van Soen 1 , Isabelle Rouaud 1 , Eric Hitti 2 , Sophie Tomasi 1
Affiliation  

In the context of research for new cytotoxic compounds, obtaining bioactive molecules from renewable sources remain a big challenge. Microorganisms and more specifically Actinobacteria from original sources are well known for their biotechnological potential and are hotspots for the discovery of new bioactive compounds. The strain DP94 studied here had shown an interesting cytotoxic activity of its culture broth (HaCaT: IC50 = 8.0 ± 1.5 μg/mL; B16: IC50 = 4.6 ± 1.8 μg/mL), which could not been explained by the compounds isolated in a previous work. The increase of the cytotoxic activity of extracts was investigated, based on a Taguchi L9 orthogonal array design, after DP94 culture in TY medium using two different vessels (bioreactor or Erlenmeyer flasks). Various culture parameters such as temperature, pH and inoculum ratio (%) were studied. For experiments conducted in a bioreactor, stirring speed was included as an additional parameter. Significant differences in the cytotoxic activities of different extracts on B16 melanoma cancer cell lines, highlighted the influence of culture temperature on the production of cytotoxic compound(s) using a bioreactor. A culture in Erlenmeyer flasks was also performed and afforded an increase of the production of the active compounds. The best conditions for the highest cytotoxicity (IC50 on B16: 6 ± 0.5 μg/mL) and the highest yield (202.0 mg/L) were identified as: pH 6, temperature 37°C and 5% inoculum.

中文翻译:

使用实验设计优化诺卡氏菌培养液的细胞毒性活性。

在研究新的细胞毒性化合物的背景下,从可再生资源获得生物活性分子仍然是一个巨大的挑战。微生物,更具体地说是原始来源的放线菌,因其生物技术潜力而众所周知,是发现新的生物活性化合物的热点。此处研究的DP94菌株显示了其培养液的有趣细胞毒性活性(HaCaT:IC50 = 8.0±1.5μg/ mL; B16:IC50 = 4.6±1.8μg/ mL),这不能通过在之前的工作。在Tatychi L9正交阵列设计的基础上,使用两个不同的容器(生物反应器或锥形瓶)在TY培养基中进行DP94培养后,研究了提取物的细胞毒性活性的增加。研究了各种培养参数,例如温度,pH和接种率(%)。对于在生物反应器中进行的实验,将搅拌速度作为附加参数包括在内。不同提取物对B16黑色素瘤癌细胞系的细胞毒性活性有显着差异,突出了培养温度对使用生物反应器产生细胞毒性化合物的影响。还进行了在锥形瓶中的培养,并增加了活性化合物的产量。确定最高细胞毒性(B16的IC50:6±0.5μg/ mL)和最高产量(202.0 mg / L)的最佳条件是:pH 6,温度37°C和5%接种量。强调了培养温度对使用生物反应器产生细胞毒性化合物的影响。还进行了在锥形瓶中的培养,并增加了活性化合物的产量。确定最高细胞毒性(B16的IC50:6±0.5μg/ mL)和最高产量(202.0 mg / L)的最佳条件是:pH 6,温度37°C和5%接种量。强调了培养温度对使用生物反应器产生细胞毒性化合物的影响。还进行了在锥形瓶中的培养,并增加了活性化合物的产量。确定最高细胞毒性(B16的IC50:6±0.5μg/ mL)和最高产量(202.0 mg / L)的最佳条件是:pH 6,温度37°C和5%接种量。
更新日期:2020-01-15
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