Indirubin and Meisoindigo in the Treatment of Chronic Myelogenous Leukemia in China

Abstract

The aim of this review is to summarize our experience and the current knowledge on the clinical results of Indirubin, a minor active constituent of a well-know traditional Chinese prescription, Ganggui Luhui Wan, and its analogue, Meisoindigo, in the treatment of chronic myelogenous leukemia (CML) in China. Indirubin and meisoindigo induced hematologic remission in patients with chronic phase (CP) CML as effective as hydroxyurea and busulfan, in addition, there were no significant differences in median duration of CP, median survival and blast crisis at 60 months from diagnosis in indirubin, meisoindigo, hydroxyurea and busulfan treated groups. However, when meisoindigo was combined with hydroxyurea, there was evidence of a significantly prolonged median duration of CP, median survival and a reduced incidence of blast crisis at 60 months compared with busulfan, meisoindigo and hydroxyurea alone. The critical mechanisms of indirubin and meisoindigo action have not yet been identified. Both antiproliferative and induced apoptosis mechanisms have been described. Further research, especially randomized trials, are required to confirm the role of indirubin and meisoindigo in the treatment of CML.

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

“…21,23 Indirubin and its derivatives have been reported to function as protein kinase inhibitors by interacting with the kinase ATP-binding pocket. 23,44,49,50 Numerous studies have also commented on its activity in maintaining the self-renewal and pluripotency of embryonic stem cells through activating the Wnt/b-catenin pathway and in promoting the proliferation of cardiomyocytes.…”

“…Anti-AR oligos (AR-ASOs) have recently been developed that effectively repress AR expression at both the mRNA and the protein level in preclinical prostate cancer models, 18,19 However, a phase 1 study of a PS LNA gapmer anti-AR-ASO in patients with advanced prostate cancer demonstrated only a limited number of PSA responses and significant dose-related toxicity. 20 In this study, we discovered that the small molecule 6-bromo-indirubin-3 0 -oxime (6BIO), an anti-leukemia indirubin derivative, 21 possesses multiple anti-prostate cancer activities. 6BIO has been reported to regulate cellular viability, proliferation, and apoptosis and act as an anti-tumor agent in a variety of human cancer models, including melanoma, 22 breast cancer, 23 bladder cancer, 24 and lymphoma.…”

An evaluation of indirubin analogues as phosphorylase kinase inhibitors

“…Indirubin (1a, Scheme 1) is a natural bis-indol molecule found in plants and mollusks [21]. It has demonstrated antileukemic properties, although the exact mechanism of this remains unclear [22]. Modifications of indirubin have lead to the discovery of other potential anticancer compounds [20,[22][23][24].…”

“…It has demonstrated antileukemic properties, although the exact mechanism of this remains unclear [22]. Modifications of indirubin have lead to the discovery of other potential anticancer compounds [20,[22][23][24]. The indirubin family of compounds target several kinases, some of which have been co-crystallised with indirubin analogues: GSK3, CDK2, CDK5, PfPK5 [18,[25][26][27][28][29][30].…”

Comparison of Two Harvesting Methods for the Continuous Production of Indigo Plant (Polygonum Tinctorium) Leaves in a Closed-Cultivation System

“…There is currently a renovated needs of indigo plants because of the demand for natural dyes and daily necessities such as soap and plastic products (Velho et al, 2017). Indigo is also used in traditional Chinese medicines to treat systemic psoriasis and leukemia (Koo & Arain, 1998;Xiao et al, 2002).…”