Dissection of mechanisms of Chinese medicinal formula Realgar- Indigo naturalis as an effective treatment for promyelocytic leukemia

Datos Bibliográficos

ID23314849
AutoresLan Wang (0000-0001-6843-476X, State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Guang‐Biao Zhou (0000-0002-6327-2316, Shanghai Jiao Tong University), Guang-Biao Zhou (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Ping Liu (0000-0002-8713-1999, State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Jun-Hong Song (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Yang Liang (0000-0002-4226-9580, State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Xiao-Jing Yan (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Fang Xu (0000-0001-8201-1595, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China; and), Bingshun Wang (0000-0002-0435-2543, Shanghai Jiao Tong University), Bing-Shun Wang (Department of Biostatistics, Shanghai Jiao Tong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, China), Jian‐Hua Mao (0000-0001-9320-6021, Shanghai Jiao Tong University), Jian-Hua Mao (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Zhi-Xiang Shen (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Sai-Juan Chen (State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China), Chen Zhu (0000-0003-3582-9022, Shanghai Jiao Tong University), Zhu Chen (0000-0002-9974-0716, State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China)
Año2008
Volumen105
Número12
Páginas4826-4831
Fecha de publicación2008-03-25
Peer ReviewedSí
Open AccessSí
TipoARTICLE
RevistaProceedings of the National Academy of Sciences (JOURNAL)
Identificadores de la revistaISSN: 0027-8424 • E-ISSN: 1091-6490
EditorialNational Academy of Sciences (PUBLISHER • US)
DOI10.1073/pnas.0712365105
PMID18344322
PMCIDPMC2290784
OpenAlexW2071479387
IdiomaEN
Citas recibidas48
Referencias citadas25

To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar- Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis , and Salvia miltiorrhiza , with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro . ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G 1 /G 0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RARα degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.

Acute promyelocytic leukemia · Biology · Cell culture · Retinoic acid · Salvia miltiorrhiza · Traditional Chinese medicine · Acute Myeloid Leukemia Research · Cancer Research · Histone Deacetylase Inhibitors Research · Medicine · Pharmacology · Retinoids in leukemia and cellular processes