title: Treatment of acute lymphoblastic leukemia from traditional chinese medicine.
abstract: Acute lymphoblastic leukemia (ALL) is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX) is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs) inhibit the thymidylate synthase (TS). Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM) as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment.
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Ya-Li
authors.identifier: 0000-0001-9952-037X
authors.initials: YL
authors.lastname: Hsiao
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Pei-Chun
authors.identifier: 0000-0002-8771-801X
authors.initials: PC
authors.lastname: Chang
authors.affiliation: School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hung-Jin
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan ; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen