Document Type

Journal Article

Department/Unit

Department of Chemistry

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a potential drug target for chemotherapy. Cryptotanshinone (CTS) was identified as a potent STAT3 inhibitor, while the effect of other tanshinones remains unknown. In this study, the influence of eight tanshinones on STAT3 activity was initially screened and isocryptotanshinone (ICTS) significantly inhibited STAT3 activity in a dual luciferase assay. ICTS inhibited the constitutive and inducible phosphorylation of STAT3 at Y705 without affecting the phosphorylation of STAT3 at S727 in A549 lung cancer cells. Furthermore, ICTS inhibited the nuclear translocation of STAT3. Compared with CTS, ICTS exhibited a stronger inhibitory effect on STAT3 phosphorylation and on A549 cytotoxicity. ICTS induced autophagy as evidenced by the accumulation of autophagic vacuoles and the increased expression of LC3 protein and autophagosomes. ICTS-induced cell death was partially reversed by the autophagy inhibitor chloroquine. The docking assay predicted that both ICTS and CTS bind the SH2 domain of STAT3. ICTS formed hydrogen bonds and pi–pi interaction with the nearby amino acid residues of Lys591, Arg609, and Ser636. These findings suggested that ICTS, a natural compound, is a potent STAT3 inhibitor. ICTS induced apoptosis and pro-death autophagy in A549 cells.

Publication Year

2016

Journal Title

Journal of Drug Targeting

Volume number

24

Issue number

10

Publisher

Informa Healthcare

First Page (page number)

934

Last Page (page number)

942

Referreed

1

DOI

10.3109/1061186X.2016.1157882

ISSN (print)

1061186X

ISSN (electronic)

10292330

Link to Publisher’s Edition

http://dx.doi.org/10.3109/1061186X.2016.1157882

Copyright

Copyright © 2017 Informa UK Limited

Keywords

Apoptosis, autophagy, isocryptotanshinone, STAT3

Available for download on Friday, December 01, 2017

Included in

Chemistry Commons

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