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 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.

Automated summary

Osteosarcoma is a challenging bone tumor to treat due to its complex nature and lack of understanding about its causes. This study combines existing literature on biological pathways in osteosarcoma with research on natural compounds to identify new targets and design more effective drug therapies. Through a Boolean network model and combinatorial circuit, the efficacy of various drugs in combination with Cryptotanshinone is predicted. The herbal drug Cryptotanshinone is shown to induce apoptosis in osteosarcoma cell lines by increasing sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) through its actions on STAT3, DRP1, and DR5. The Boolean framework is used to identify additional drug intervention points in the pathway that could enhance the effects of Cryptotanshinone.