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

Lan Wang, Guang Biao Zhou, Ping Liu, Jun Hong Song, Yang Liang, Xiao Jing Yan, Fang Xu, Bing Shun Wang, Jian Hua Mao, Zhi Xiang Shen, Sai Juan Chen, Zhu Chen

Research output: Contribution to journalArticle

522 Citations (Scopus)

Abstract

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 G1/G0 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.

Original languageEnglish (US)
Pages (from-to)4826-4831
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number12
DOIs
StatePublished - Mar 25 2008
Externally publishedYes

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Acute Promyelocytic Leukemia
Dissection
Leukemia
Retinoic Acid Receptors
Aquaglyceroporins
Salvia miltiorrhiza
Therapeutics
Ubiquitination
Oncogene Proteins
Chinese Traditional Medicine
Traditional Medicine
Minerals
Cell Differentiation
realgar-indigo naturalis

Keywords

  • Active ingredient
  • Synergism
  • Systems biology
  • Tetraarsenic tetrasulfide
  • Traditional Chinese medicine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. / Wang, Lan; Zhou, Guang Biao; Liu, Ping; Song, Jun Hong; Liang, Yang; Yan, Xiao Jing; Xu, Fang; Wang, Bing Shun; Mao, Jian Hua; Shen, Zhi Xiang; Chen, Sai Juan; Chen, Zhu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 12, 25.03.2008, p. 4826-4831.

Research output: Contribution to journalArticle

Wang, Lan ; Zhou, Guang Biao ; Liu, Ping ; Song, Jun Hong ; Liang, Yang ; Yan, Xiao Jing ; Xu, Fang ; Wang, Bing Shun ; Mao, Jian Hua ; Shen, Zhi Xiang ; Chen, Sai Juan ; Chen, Zhu. / Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 12. pp. 4826-4831.
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AU - Wang, Lan

AU - Zhou, Guang Biao

AU - Liu, Ping

AU - Song, Jun Hong

AU - Liang, Yang

AU - Yan, Xiao Jing

AU - Xu, Fang

AU - Wang, Bing Shun

AU - Mao, Jian Hua

AU - Shen, Zhi Xiang

AU - Chen, Sai Juan

AU - Chen, Zhu

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