Anti-tumor effects of cryptotanshinone (C19H20O3) in human osteosarcoma cell lines

Biomedicine & Pharmacotherapy

Jianping Hua¹  Chao Sima²  Aniruddha Datta³  Michael Bittner³  Rosana Lopes⁴  Haswanth Vundavilli⁴  Heather M. Wilson-Robles⁵  Tasha Miller⁵ 

[1] Corresponding author at: Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA.;Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;The Center for Bioinformatics and Genomic Systems Engineering, TEES/Texas A&M University, College Station, TX, USA;Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA;The Center for Bioinformatics and Genomic Systems Engineering, TEES/Texas A&M University, College Station, TX, USA;

关键词: Osteosarcoma;    Cancer modeling;    Differential equations;    Cryptotanshinone;    Chemotherapy;    Gene regulatory networks;   

DOI  :  

来源: DOAJ

【 摘 要 】

Osteosarcoma is the most prevalent malignant bone tumor and occurs most commonly in the adolescent and young adult population. Despite the recent advances in surgeries and chemotherapy, the overall survival in patients with resectable metastases is around 20%. This challenge in osteosarcoma is often attributed to the drastic differences in the tumorigenic profiles and mutations among patients. With diverse mutations and multiple oncogenes, it is necessary to identify the therapies that can attack various mutations and simultaneously have minor side-effects. In this paper, we constructed the osteosarcoma pathway from literature and modeled it using ordinary differential equations. We then simulated this network for every possible gene mutation and their combinations and ranked different drug combinations based on their efficacy to drive a mutated osteosarcoma network towards cell death. Our theoretical results predict that drug combinations with Cryptotanshinone (C19H20O3), a traditional Chinese herb derivative, have the best overall performance. Specifically, Cryptotanshinone in combination with Temsirolimus inhibit the JAK/STAT, MAPK/ERK, and PI3K/Akt/mTOR pathways and induce cell death in tumor cells. We corroborated our theoretical predictions using wet-lab experiments on SaOS2, 143B, G292, and HU03N1 human osteosarcoma cell lines, thereby demonstrating the potency of Cryptotanshinone in fighting osteosarcoma.

【 授权许可】

Unknown