2. Academic Validation
  3. Methyllucidone inhibits STAT3 activity by regulating the expression of the protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells

Methyllucidone inhibits STAT3 activity by regulating the expression of the protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells

  • Bioorg Med Chem Lett. 2018 Mar 1;28(5):853-857. doi: 10.1016/j.bmcl.2018.02.012.
Yena Jin 1,  Young Hwan Kim 2,  Jin Yong Park 1,  Yu-Jin Lee 3,  Hyun-Mi Oh 3,  Sung-Kyu Choi 3,  Dong Cho Han 4,  Byoung-Mog Kwon 5
Affiliations

Affiliations

  • 1 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Korea University of Science and Technology, Daejeon, Republic of Korea.
  • 2 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
  • 3 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
  • 4 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Korea University of Science and Technology, Daejeon, Republic of Korea. Electronic address: dchan@kribb.re.kr.
  • 5 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Korea University of Science and Technology, Daejeon, Republic of Korea. Electronic address: kwonbm@kribb.re.kr.
PMID: 29456111 DOI: 10.1016/j.bmcl.2018.02.012
Abstract

During the search for signal transducer and activator of transcription 3 (STAT3) inhibitors from Natural Products, methyllucidone, isolated from Lindera species (Lauraceae), was identified as a STAT3 Inhibitor. Methyllucidone inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU145 prostate Cancer cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in LNCaP cells. Methyllucidone decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, Bcl-2, Mcl-1, and Survivin. Methyllucidone inhibited DU145 cell growth and induced Apoptosis by arresting the cell cycle at G1 phase. Notably, knockdown of the MEG2 gene by small interfering RNA suppressed the ability of methyllucidone to inhibit STAT3 activation. Methyllucidone regulates STAT3 activity by modulating MEG2 expression, and our results suggest that this compound is a novel inhibitor of the STAT3 pathway and may be a useful lead molecule for the development of a therapeutic STAT3 Inhibitor.

Keywords

Apoptosis; MEG2 phosphatase; Methyllucidone; Prostate cancer; STAT3.

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