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Anti-Leukemic Effects of Idesia polycarpa Maxim Branch on Human B-Cell Acute Lymphoblastic Leukemia Cells

Authors :
Chan-Seong Kwon
Ji-Eun Lee
Byeol-Eun Jeon
Ye-Rin Woo
Yun-Seo Kim
Jae-Woo Kim
Chae-Jin Park
Seo-Yun Jang
Sang-Woo Kim
Source :
Current Issues in Molecular Biology, Vol 45, Iss 5, Pp 4035-4049 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Patients with pediatric B-cell acute lymphoblastic leukemia (B-ALL) have a high survival rate, yet the prognosis of adults and patients with relapsed/refractory disease is relatively poor. Therefore, it is imperative to develop new therapeutic strategies. Here, we screened 100 plant extracts from South Korean Flora and investigated their anti-leukemic effect using CCRF-SB cells as a B-ALL model. The top cytotoxic extract identified in this screening was the Idesia polycarpa Maxim. branch (IMB), which efficiently inhibited the survival and proliferation of CCRF-SB cells, while having minimal to no impact on normal murine bone marrow cells. Mechanistically, the IMB-induced proapoptotic effect involves the increase of caspase 3/7 activity, which was shown to be associated with the disruption of the mitochondrial membrane potential (MMP) through the reduction in antiapoptotic Bcl-2 family expression. IMB also promoted the differentiation of CCRF-SB cells via the upregulation of the expression of differentiation-related genes, PAX5 and IKZF1. Given that resistance to glucocorticoid (GC) is often found in patients with relapsed/refractory ALL, we investigated whether IMB could restore GC sensitivity. IMB synergized GC to enhance apoptotic rate by increasing GC receptor expression and downmodulating mTOR and MAPK signals in CCRF-SB B-ALL cells. These results suggest that IMB has the potential to be a novel candidate for the treatment of B-ALL.

Details

Language :
English
ISSN :
14673045 and 14673037
Volume :
45
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Current Issues in Molecular Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.17ad180fb874733adc167d7c748594e
Document Type :
article
Full Text :
https://doi.org/10.3390/cimb45050257