Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy

Hongfeng Yuan, Meilan He, Fan Cheng, Rosemary Bai, Suzane Ramos da Silva, Ricardo C T Aguiar, Shou Jiang Gao

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where tenovin-6 was used as an inhibitor of sirtuins.

Original languageEnglish (US)
Pages (from-to)14912-14924
Number of pages13
JournalOncotarget
Volume8
Issue number9
DOIs
StatePublished - 2017

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Autophagy
Sirtuins
Light
Microtubule-Associated Proteins
Hematologic Neoplasms
Therapeutics
tenovin-6
Non-Hodgkin's Lymphoma
Cell Survival
Cell Proliferation
Recurrence
Cell Line
Pharmaceutical Preparations
Genes

Keywords

  • Autophagy
  • Diffuse large B-cell lymphoma
  • P53
  • Sirtuins
  • Tenovin-6

ASJC Scopus subject areas

  • Oncology

Cite this

Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. / Yuan, Hongfeng; He, Meilan; Cheng, Fan; Bai, Rosemary; da Silva, Suzane Ramos; Aguiar, Ricardo C T; Gao, Shou Jiang.

In: Oncotarget, Vol. 8, No. 9, 2017, p. 14912-14924.

Research output: Contribution to journalArticle

Yuan, Hongfeng ; He, Meilan ; Cheng, Fan ; Bai, Rosemary ; da Silva, Suzane Ramos ; Aguiar, Ricardo C T ; Gao, Shou Jiang. / Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. In: Oncotarget. 2017 ; Vol. 8, No. 9. pp. 14912-14924.
@article{09a6f9508086405193f73bf80a43e636,
title = "Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy",
abstract = "Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where tenovin-6 was used as an inhibitor of sirtuins.",
keywords = "Autophagy, Diffuse large B-cell lymphoma, P53, Sirtuins, Tenovin-6",
author = "Hongfeng Yuan and Meilan He and Fan Cheng and Rosemary Bai and {da Silva}, {Suzane Ramos} and Aguiar, {Ricardo C T} and Gao, {Shou Jiang}",
year = "2017",
doi = "10.18632/oncotarget.14741",
language = "English (US)",
volume = "8",
pages = "14912--14924",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "9",

}

TY - JOUR

T1 - Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy

AU - Yuan, Hongfeng

AU - He, Meilan

AU - Cheng, Fan

AU - Bai, Rosemary

AU - da Silva, Suzane Ramos

AU - Aguiar, Ricardo C T

AU - Gao, Shou Jiang

PY - 2017

Y1 - 2017

N2 - Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where tenovin-6 was used as an inhibitor of sirtuins.

AB - Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where tenovin-6 was used as an inhibitor of sirtuins.

KW - Autophagy

KW - Diffuse large B-cell lymphoma

KW - P53

KW - Sirtuins

KW - Tenovin-6

UR - http://www.scopus.com/inward/record.url?scp=85014092217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014092217&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.14741

DO - 10.18632/oncotarget.14741

M3 - Article

AN - SCOPUS:85014092217

VL - 8

SP - 14912

EP - 14924

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 9

ER -