Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells

Shuhui Guo, Weiwei Luo, Lijuan Liu, Xiaocong Pang, Hong Zhu, Ailin Liu, Jinjian Lu, Dik-Lung Ma, Chung Hang Leung, Yitao Wang, Xiuping Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

33 Citations (Scopus)
20 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)934-942
Number of pages9
JournalJournal of Drug Targeting
Issue number10
Early online date27 Mar 2016
Publication statusPublished - Nov 2016

Scopus Subject Areas

  • Pharmaceutical Science

User-Defined Keywords

  • Apoptosis
  • autophagy
  • isocryptotanshinone
  • STAT3


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