Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation

Abstract

Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains

“…Therefore, some ingredients may inactivate tumor suppressors, but others may work as demethylating reagents. At the same time, many TCMs have been reported to be used as demethylating reagents [ 25 ].…”

Clinical Response to Traditional Chinese Herbs Containing Realgar (As2S2) is Related to DNA Methylation Patterns in Bone Marrow DNA from Patients with Myelodysplastic Syndrome with Multilineage Dysplasia

“…The overall response rate to the realgar-based treatment was 81.53% (106/130) for hematologic improvement in patients with MDS-MLD. 4 We have also recently reported that the clinical efficacy of CHs was related to the concentration of arsenic in the peripheral blood, and that increasing the arsenic concentration to over 20 μg/L had potential as a therapeutic strategy for treating MDS-MLD patients. 5 However, some MDS-MLD patients do not respond to treatment, even at arsenic concentrations greater than 20 μg/L, which suggested that other factors could also influence the efficacy of CHs.…”

“…3 Consequently, finding effective therapeutic drugs from traditional medicines has become an important strategy for the curing of MDS. 4,5 Traditional Chinese medicine (TCM) is characterized by a special theory (see Discussion below) and has been applied in China for more than 3000 years. In 1979, Tingdong Zhang, a TCM doctor, reported for the first time that acute promyelocytic leukemia (APL) could be treated effectively with an injection, the main constituent drug of which was arsenic trioxide (ATO).…”