Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma

Kok-Tong Tan, Meng-Xian Lin, Shih-Chao Lin, Yu-Tang Tung, Sheng-Hao Lin, Chi-Chien Lin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.

Original languageEnglish
JournalAnti-Cancer Drugs
DOIs
Publication statusE-pub ahead of print - Jan 29 2019

Fingerprint

T-Cell Lymphoma
Autophagy
Jurkat Cells
Apoptosis
JNK Mitogen-Activated Protein Kinases
Therapeutics
Reactive Oxygen Species
T-Cell Leukemia
Poly(ADP-ribose) Polymerases
sinensetin
Caspase 8
Mitochondrial Membrane Potential
Drug Delivery Systems
Vacuoles
Caspase 3
Antineoplastic Agents
Cell Death
Up-Regulation
Down-Regulation
Cell Proliferation

Cite this

Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma. / Tan, Kok-Tong; Lin, Meng-Xian; Lin, Shih-Chao; Tung, Yu-Tang; Lin, Sheng-Hao; Lin, Chi-Chien.

In: Anti-Cancer Drugs, 29.01.2019.

Research output: Contribution to journalArticle

Tan, Kok-Tong ; Lin, Meng-Xian ; Lin, Shih-Chao ; Tung, Yu-Tang ; Lin, Sheng-Hao ; Lin, Chi-Chien. / Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma. In: Anti-Cancer Drugs. 2019.
@article{4b4da2e6eced429fad8b1269124d7d18,
title = "Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma",
abstract = "The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.",
author = "Kok-Tong Tan and Meng-Xian Lin and Shih-Chao Lin and Yu-Tang Tung and Sheng-Hao Lin and Chi-Chien Lin",
year = "2019",
month = "1",
day = "29",
doi = "10.1097/CAD.0000000000000756",
language = "English",
journal = "Anti-Cancer Drugs",
issn = "0959-4973",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma

AU - Tan, Kok-Tong

AU - Lin, Meng-Xian

AU - Lin, Shih-Chao

AU - Tung, Yu-Tang

AU - Lin, Sheng-Hao

AU - Lin, Chi-Chien

PY - 2019/1/29

Y1 - 2019/1/29

N2 - The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.

AB - The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.

U2 - 10.1097/CAD.0000000000000756

DO - 10.1097/CAD.0000000000000756

M3 - Article

C2 - 30702500

JO - Anti-Cancer Drugs

JF - Anti-Cancer Drugs

SN - 0959-4973

ER -