Reference Detail

Ref Type

Journal Article

PMID

(26655844)

Authors

Chini CC, Espindola-Netto JM, Mondal G, Guerrico AM, Nin V, Escande C, Sola-Penna M, Zhang JS, Billadeau DD, Chini EN

Title

SIRT1-Activating Compounds (STAC) Negatively Regulate Pancreatic Cancer Cell Growth and Viability Through a SIRT1 Lysosomal-Dependent Pathway.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	22	10	2016 May 15	2496-507	Clin Cancer Res

URL

Abstract Text

Recent studies suggest that SIRT1-activating compounds (STAC) are a promising class of anticancer drugs, although their mechanism of action remains elusive. The main goal of this study is to determine the role of STACs as a potential therapy for pancreatic cancer. In addition, we also explored the mechanism by which these compounds affect pancreatic cancer.Using in vitro (cell culture experiments) and in vivo (xenograft experiments) approaches, we studied the role of SIRT1 agonists (STAC) in human pancreatic cancer cell viability and growth.We show that SIRT1 is highly expressed in pancreatic cancer cells and that the STACs SRT1720, SRT1460, and SRT3025 inhibited cell growth and survival of pancreatic cancer cells. STACs enhanced the sensitivity of pancreatic cells to gemcitabine and paclitaxel, indicating that these drugs could be used in combination with other chemotherapy drugs. We also show that STACs were very effective in inhibiting tumor xenograft growth. In mechanistic studies, we observed that STACs activated a SIRT1 lysosomal-dependent cell death. Furthermore, the effect of STACs on cell viability was also dependent on the expression of the endogenous SIRT1 inhibitor DBC1.Taken together, our results reveal an essential role for SIRT1 and lysosomes in the death pathway regulated by STACs in pancreatic cancer cells. Clin Cancer Res; 22(10); 2496-507. ©2015 AACR.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
SRT1460	SRT1460	0	0
SRT1720	SRT1720	0	0
SRT3025	SRT3025	0	0

Drug Name	Drug Classes	Drug Description
SRT1460	SIRT1 Activator 3	SRT1460 is a SIRT1 activator, which may decrease tumor cell growth and enhance sensitivity to other anti-cancer agents (PMID: 26655844, PMID: 27334466).
SRT1720	SIRT1 Activator 3	SRT1720 is a SIRT1 activator, which potentially results in increased tumor cell death and decreased tumor growth, and may enhance sensitivity to other anti-cancer agents (PMID: 26655844, PMID: 32421926).
SRT3025	SIRT1 Activator 3	SRT3025 is a SIRT1 activator, which may lead to decreased tumor growth and increased senstivity to other anti-cancer agents (PMID: 26655844, PMID: 31141802).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References