LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473
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作者:
Zhang, Yuanjiao
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Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Zhang, Yuanjiao
[1
,2
]
Qian, Jiacheng
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Nanjing Univ Chinese Med, State Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Qian, Jiacheng
[3
]
Jiang, Mingmei
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Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Jiang, Mingmei
[1
,2
]
Yang, Shu
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Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Yang, Shu
[1
,2
]
Zhou, Lianxin
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Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Zhou, Lianxin
[1
,2
]
Zhang, Qin
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Nanjing Univ Chinese Med, Dept Gynecol, Jiangsu Prov Hosp, Affiliated Hosp, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Zhang, Qin
[4
]
Lin, Liping
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Nanjing Univ Chinese Med, State Key Lab Cultivat Base TCM Qual & Efficacy, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Lin, Liping
[3
]
Yang, Ye
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Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing, Peoples R ChinaNanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Nanjing, Peoples R China
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
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.
机构:
Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Koide, Hiroyuki
Asai, Tomohiro
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Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Asai, Tomohiro
Furuya, Keiichi
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Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Furuya, Keiichi
Tsuzuku, Takuma
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机构:
Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Tsuzuku, Takuma
Kato, Hiroki
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机构:
Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Kato, Hiroki
Dewa, Takehisa
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Nagoya Inst Technol, Showa Ku, Nagoya, Aichi 4668555, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Dewa, Takehisa
Nango, Mamoru
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Nagoya Inst Technol, Showa Ku, Nagoya, Aichi 4668555, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Nango, Mamoru
Maeda, Noriyuki
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机构:
Nippon Fine Chem Co Ltd, Takasago, Hyogo 6760074, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Maeda, Noriyuki
Oku, Naoto
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Univ Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
Univ Shizuoka, Global COE Program, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, JapanUniv Shizuoka, Dept Med Biochem, Grad Sch Pharmaceut Sci, Suruga Ku, Shizuoka 4228526, Japan
机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Chen, G.
Han, K.
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Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Han, K.
Xu, X.
论文数: 0引用数: 0
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机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Xu, X.
Du, X.
论文数: 0引用数: 0
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Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Du, X.
Zhang, Z.
论文数: 0引用数: 0
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Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Zhang, Z.
Tang, J.
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机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Tang, J.
Shi, M.
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机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Shi, M.
Wang, M.
论文数: 0引用数: 0
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机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Wang, M.
Li, J.
论文数: 0引用数: 0
h-index: 0
机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Li, J.
Cao, B.
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机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Cao, B.
Mao, X.
论文数: 0引用数: 0
h-index: 0
机构:
Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
Soochow Univ, Dept Pharmacol, Coll Pharm, Suzhou 215123, Peoples R ChinaSoochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China