In Silico Modeling of the Induction of Apoptosis by Cryptotanshinone in Osteosarcoma Cell Lines

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 ab...

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Bibliographic Details
Published in:IEEE/ACM transactions on computational biology and bioinformatics 2022-05, Vol.19 (3), p.1683-1693
Main Authors: Saraf, Radhika, Datta, Aniruddha, Sima, Chao, Hua, Jianping, Lopes, Rosana, Bittner, Michael L., Miller, Tasha, Wilson-Robles, Heather M.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bioinformatics
Biomedical materials
Bone cancer
Bone Neoplasms - drug therapy
Bone Neoplasms - metabolism
Bone Neoplasms - pathology
Bone tumors
Boolean
Boolean algebra
Boolean networks
Cancer
Cell Line, Tumor
Circuit faults
Circuits
Combinatorial analysis
Computer Simulation
Cryptography
Cryptotanshinone
Dogs
Drug development
drug targets
Drugs
Etiology
Genomic instability
Herbal medicine
Osteosarcoma
Osteosarcoma - drug therapy
Osteosarcoma - metabolism
Osteosarcoma - pathology
Phenanthrenes
simulation and modeling
Stat3 protein
Target recognition
TRAIL protein
Tumor necrosis factor
Tumors
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Summary: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.
ISSN:1545-5963
1557-9964
DOI:10.1109/TCBB.2020.3037318