LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473

被引:0
|
作者
Zhang, Yuanjiao [1 ,2 ]
Qian, Jiacheng [3 ]
Jiang, Mingmei [1 ,2 ]
Yang, Shu [1 ,2 ]
Zhou, Lianxin [1 ,2 ]
Zhang, Qin [4 ]
Lin, Liping [3 ]
Yang, Ye [1 ,2 ]
机构
[1] Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
[2] Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R China
[3] Nanjing Univ Chinese Med, State Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing, Peoples R China
[4] Nanjing Univ Chinese Med, Dept Gynecol, Jiangsu Prov Hosp, Affiliated Hosp, Nanjing, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2023年 / 13卷
基金
中国国家自然科学基金;
关键词
multiple myeloma; indole oligomer; LTe2; Akt; phosphorylation; apoptosis; TUMOR-GROWTH; PROTEASOME; DIAGNOSIS; PATHWAY;
D O I
10.3389/fonc.2023.1269670
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possesses a wide range of anticancer activities through various mechanisms. Here, we aim to explore the anti-tumor efficiency and potential downstream targets of LTe2 in MM. Its bioactivity was assessed by employing MTT assays, flow cytometry, and the 5TMM3VT mouse model. Additionally, transcriptomic RNA-seq analysis and molecular dynamics (MD) experiments were conducted to elucidate the mechanism underlying LTe2 induced MM cell apoptosis. The results demonstrated that LTe2 significantly inhibited MM cell proliferation both in vitro and in vivo, and revealed that LTe2 exerts its effect by inhibiting the phosphorylation of AKT at the Thr308 and Ser473 sites. In summary, our findings highlight the potential of LTe2 as a novel candidate drug for MM treatment and provided a solid foundation for future clinical trials involving LTe2.
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页数:11
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