In Silico Modeling of the Induction of Apoptosis by Cryptotanshinone in Osteosarcoma Cell Lines
In Silico Modeling of the Induction of Apoptosis by Cryptotanshinone in Osteosarcoma Cell Lines
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DOI：
10.1109/tcbb.2020.3037318
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Radhika Saraf;A. Datta;Chao Sima;Jianping Hua;Rosana Lopes;M. Bittner;T. Miller;H. Wilson-Robles
中科院分区：
文献类型：
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作者：
Radhika Saraf;A. Datta;Chao Sima;Jianping Hua;Rosana Lopes;M. Bittner;T. Miller;H. Wilson-Robles
骨肉瘤(OS)是儿童和宠物犬最常见的原发恶性骨肿瘤。其特有的基因组不稳定性和复杂性，加上对其病因学知识的缺乏，使得目前的治疗方法难以改进。我们利用已有的关于OS中活跃的生物通路的文献，并将其与目前涉及天然化合物的研究相结合，以确定新的靶点，并设计更有效的药物疗法。这些通路的关键部件被建模为具有多个输入和多个输出的布尔网络。利用组合电路从理论上预测了各种药物与隐丹参酮的联合作用效果。我们发现，中药隐丹参酮通过对STAT3、DRp1和DR5的多管齐下作用，增加对肿瘤坏死因子相关的凋亡诱导配体(TRAIL)的敏感性，从而诱导OS细胞的凋亡。布尔框架被用来检测可能放大隐丹参酮作用的途径中的额外药物干预点。
Osteosarcoma (OS) is the most common primary malignant bone tumor of both children and pet canines. Its characteristic genomic instability and complexity coupled with the dearth of knowledge about its etiology has made improvement in the current treatment difficult. We use the existing literature about the biological pathways active in OS and combine it with the current research involving natural compounds to identify new targets and design more effective drug therapies. The key components of these pathways are modeled as a Boolean network with multiple inputs and multiple outputs. The combinatorial circuit is employed to theoretically predict the efficacies of various drugs in combination with Cryptotanshinone. We show that the action of the herbal drug, Cryptotanshinone on OS cell lines induces apoptosis by increasing sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) through its multi-pronged action on STAT3, DRP1 and DR5. The Boolean framework is used to detect additional drug intervention points in the pathway that could amplify the action of Cryptotanshinone.