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.
引用
收藏
页数:11
相关论文
共 50 条
  • [31] CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site
    Zhuo, De-Xiang
    Zhang, Xiao-Wei
    Jin, Bo
    Zhang, Zheng
    Xie, Bu-Shan
    Wu, Cheng-Lin
    Gong, Kan
    Mao, Ze-Bin
    [J]. PLOS ONE, 2013, 8 (06):
  • [32] Monotropein alleviates septic acute liver injury by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway
    Xie, Kunmei
    Wang, Feibiao
    Yang, Yue
    Pan, Shoujie
    Wang, Junyao
    Xiao, Nan
    Wang, Xinyan
    Ma, Zhihao
    Xu, Xiaolong
    Dong, Zibo
    [J]. INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 142
  • [33] The oral PKC-β inhibitor enzastaurin (LY317615) suppress phosphorylation and induces apoptosis in multiple myeloma cell lines by inhibition of AKT pathway.
    Neri, Antonino
    Marmiroli, Sandra
    Tassone, Pierfrancesco
    Lombardi, Luigia
    Nobili, Lucia
    Verdelli, Donata
    Civallero, Monica
    Cosenza, Maria
    Bertacchini, Jessika
    Federico, Massimo
    De Pol, Anto
    Deliliers, Giorgio Lambertenghi
    Sacchi, Stefano
    [J]. BLOOD, 2006, 108 (11) : 400A - 400A
  • [34] Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55α regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt
    Kuo, Yi-Chun
    Huang, Kai-Yun
    Yang, Chung-Hsiang
    Yang, Yu-San
    Lee, Wen-Yu
    Chiang, Chi-Wu
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (04) : 1882 - 1892
  • [35] Inhibition of Akt (ser473) Phosphorylation and Rapamycin-Resistant Cell Growth by Knockdown of Mammalian Target of Rapamycin with Small Interfering RNA in Vascular Endothelial Growth Factor Receptor-1-Targeting Vector
    Koide, Hiroyuki
    Asai, Tomohiro
    Furuya, Keiichi
    Tsuzuku, Takuma
    Kato, Hiroki
    Dewa, Takehisa
    Nango, Mamoru
    Maeda, Noriyuki
    Oku, Naoto
    [J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2011, 34 (05) : 602 - 608
  • [36] Mangiferin induces apoptosis in multiple myeloma cell lines by suppressing the activation of nuclear factor kappa B-inducing kinase
    Takeda, Tomoya
    Tsubaki, Masanobu
    Kino, Toshiki
    Yamagishi, Misa
    Iida, Megumi
    Itoh, Tatsuki
    Imano, Motohiro
    Tanabe, Genzoh
    Muraoka, Osamu
    Satou, Takao
    Nishida, Shozo
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 2016, 251 : 26 - 33
  • [37] An anti-leishmanial thiadiazine agent induces multiple myeloma cell apoptosis by suppressing the nuclear factor kappaB signalling pathway
    Chen, G.
    Han, K.
    Xu, X.
    Du, X.
    Zhang, Z.
    Tang, J.
    Shi, M.
    Wang, M.
    Li, J.
    Cao, B.
    Mao, X.
    [J]. BRITISH JOURNAL OF CANCER, 2014, 110 (01) : 63 - 70
  • [38] An anti-leishmanial thiadiazine agent induces multiple myeloma cell apoptosis by suppressing the nuclear factor kappaB signalling pathway
    G Chen
    K Han
    X Xu
    X Du
    Z Zhang
    J Tang
    M Shi
    M Wang
    J Li
    B Cao
    X Mao
    [J]. British Journal of Cancer, 2014, 110 : 63 - 70
  • [39] Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway
    Kuttikrishnan, Shilpa
    Ahmad, Fareed
    Mateo, Jericha M.
    Prabhu, Kirti S.
    El-Elimat, Tamam
    Oberlies, Nicholas H.
    Pearce, Cedric J.
    Akil, Ammira S. Alshabeeb
    Bhat, Ajaz A.
    Alali, Feras Q.
    Uddin, Shahab
    [J]. CELL BIOLOGY INTERNATIONAL, 2024, 48 (02) : 190 - 200
  • [40] Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines
    Rizvi, Mujahid A.
    Ghias, Kulsoom
    Davies, Katharine M.
    Ma, Chunguang
    Weinberg, Frank
    Munshi, Hidayatullah G.
    Krett, Nancy L.
    Rosen, Steven T.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2006, 5 (07) : 1783 - 1789