2. Academic Validation
  3. Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells

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

  • J Drug Target. 2016 Dec;24(10):934-942. doi: 10.3109/1061186X.2016.1157882.
Shuhui Guo 1,  Weiwei Luo 1,  Lijuan Liu 1,  Xiaocong Pang 2,  Hong Zhu 3,  Ailin Liu 2,  Jinjian Lu 1,  Dik-Lung Ma 4,  Chung-Hang Leung 1,  Yitao Wang 1,  Xiuping Chen 1
Affiliations

Affiliations

  • 1 a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macau , China.
  • 2 b Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
  • 3 c Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences , Zhejiang University , Hangzhou , Zhejiang , China.
  • 4 d Department of Chemistry , Hong Kong Baptist University , Kowloon Tong , Hong Kong.
PMID: 26904961 DOI: 10.3109/1061186X.2016.1157882
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.

Keywords

Apoptosis; STAT3; autophagy; isocryptotanshinone.

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