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Assessment of cytotoxic and genotoxic potentials of a mononuclear Fe(II) Schiff base complex with photocatalytic activity in Trigonella.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.bbagen.2019.129503 Kalyan Mahapatra 1 , Ayon Kanti Ghosh 2 , Sayanti De 1 , Noyel Ghosh 3 , Pritam Sadhukhan 3 , Sharmistha Chatterjee 3 , Rajarshi Ghosh 2 , Parames C Sil 3 , Sujit Roy 1
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.bbagen.2019.129503 Kalyan Mahapatra 1 , Ayon Kanti Ghosh 2 , Sayanti De 1 , Noyel Ghosh 3 , Pritam Sadhukhan 3 , Sharmistha Chatterjee 3 , Rajarshi Ghosh 2 , Parames C Sil 3 , Sujit Roy 1
Affiliation
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BACKGROUND
In recent times, coordination complexes of iron in various oxidation states along with variety of ligand systems have been designed and developed for effective treatment of cancer cells without adversely affecting the normal cell and tissues of various organs.
METHODS
In this study, we have evaluated the mechanism of action of a Fe(II) Schiff base complex in the crop plant Trigonella foenum-graecum L. (Fenugreek) as the screening system by using morphological, cytological, biochemical and molecular approaches. Further functional characterization was performed using MCF-7 cell line and solid tumour model for the assessment of anti-tumour activity of the complex.
RESULTS
Our results indicate efficiency of the Fe(II) Schiff base complex in the induction of double strand breaks in DNA. Complex treatment clearly induced cytotoxic and genotoxic damage in Trigonella seedlings. The Fe-complex treatment caused cell cycle arrest via the activation of ATM-ATR kinase mediated DNA damage response pathway with the compromised expression of CDK1, CDK2 and CyclinB1 protein in Trigonella seedlings. In cultured MCF-7 cells, the complex induces cytotoxicity and DNA fragmentation through intracellular ROS generation. Fe-complex treatment inhibited tumour growth in solid tumour model with no additional side effects.
CONCLUSION
The growth inhibitory and cytotoxic effects of the complex result from activation of DNA damage response along with oxidative stress and cell cycle arrest.
GENERAL SIGNIFICANCE
Overall, our results have provided comprehensive information on the mechanism of action and efficacy of a Fe(II) Schiff base complex in higher eukaryotic genomes and indicated its future implications as potential therapeutic agent.
中文翻译：
评估具有光催化活性的单核铁（II）席夫碱复合物在Trigonella中的细胞毒性和遗传毒性潜力。
背景技术近来，已经设计和开发了各种氧化态的铁的配位络合物以及各种配体系统，以有效治疗癌细胞而不会不利地影响各种器官的正常细胞和组织。方法在本研究中，我们通过形态学，细胞学，生化和分子学方法，评估了铁（II）席夫碱复合物在农作物三角叶草（胡芦巴）作为筛选系统中的作用机理。使用MCF-7细胞系和实体瘤模型进行进一步的功能表征，以评估复合物的抗肿瘤活性。结果我们的结果表明，Fe（II）Schiff碱复合物在诱导DNA双链断裂中的效率。复合处理明显地引起了Trigonella幼苗中的细胞毒性和遗传毒性损害。铁复合物处理通过激活ATM-ATR激酶介导的DNA损伤反应途径而导致细胞周期停滞，其中Trigonella幼苗中CDK1，CDK2和CyclinB1蛋白的表达受到损害。在培养的MCF-7细胞中，该复合物通过细胞内ROS的产生诱导细胞毒性和DNA片段化。铁络合物治疗可抑制实体瘤模型中的肿瘤生长，且无其他副作用。结论复合物的生长抑制和细胞毒性作用是由于DNA损伤反应的激活以及氧化应激和细胞周期停滞引起的。一般意义总体而言，
更新日期：2019-12-07
中文翻译：
评估具有光催化活性的单核铁（II）席夫碱复合物在Trigonella中的细胞毒性和遗传毒性潜力。
背景技术近来，已经设计和开发了各种氧化态的铁的配位络合物以及各种配体系统，以有效治疗癌细胞而不会不利地影响各种器官的正常细胞和组织。方法在本研究中，我们通过形态学，细胞学，生化和分子学方法，评估了铁（II）席夫碱复合物在农作物三角叶草（胡芦巴）作为筛选系统中的作用机理。使用MCF-7细胞系和实体瘤模型进行进一步的功能表征，以评估复合物的抗肿瘤活性。结果我们的结果表明，Fe（II）Schiff碱复合物在诱导DNA双链断裂中的效率。复合处理明显地引起了Trigonella幼苗中的细胞毒性和遗传毒性损害。铁复合物处理通过激活ATM-ATR激酶介导的DNA损伤反应途径而导致细胞周期停滞，其中Trigonella幼苗中CDK1，CDK2和CyclinB1蛋白的表达受到损害。在培养的MCF-7细胞中，该复合物通过细胞内ROS的产生诱导细胞毒性和DNA片段化。铁络合物治疗可抑制实体瘤模型中的肿瘤生长，且无其他副作用。结论复合物的生长抑制和细胞毒性作用是由于DNA损伤反应的激活以及氧化应激和细胞周期停滞引起的。一般意义总体而言，
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