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

被引:4
|
作者
Kwon, Chan-Seong [1 ]
Lee, Ji-Eun [1 ]
Jeon, Byeol-Eun [1 ]
Woo, Ye-Rin [1 ]
Kim, Yun-Seo [2 ]
Kim, Jae-Woo [2 ]
Park, Chae-Jin [2 ]
Jang, Seo-Yun [2 ]
Kim, Sang-Woo [1 ,2 ]
机构
[1] Pusan Natl Univ, Dept Integrated Biol Sci, Busan 46241, South Korea
[2] Pusan Natl Univ, Dept Biol Sci, Busan 46241, South Korea
基金
新加坡国家研究基金会;
关键词
B-cell acute lymphoblastic leukemia; Idesia polycarpa Maxim branch; anti-leukemic effect; differentiation; glucocorticoid resistance; INDUCED APOPTOSIS; DIFFERENTIATION; RAPAMYCIN; INDUCTION; THERAPY; CANCER; ADULTS; TRIAL; MTOR;
D O I
10.3390/cimb45050257
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4035 / 4049
页数:15
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