Capillarisin inhibits constitutive and inducible STAT3 activation through induction of SHP-1 and SHP-2 tyrosine phosphatases

Cancer Letters
Jong Hyun LeeKwang Seok Ahn

Abstract

Signal transducers and activators of transcription (STAT)-3 is a latent cytosolic transcription factor that has been closely associated with survival, proliferation, chemoresistance, and metastasis of tumor cells. Whether the anti-proliferative, pro-apoptotic, and anti-metastatic effects of capillarisin (CPS), derived from Artemisia capillaris (Compositae), are linked to its capability to inhibit STAT3 activation was investigated. We found that CPS specifically inhibited both constitutive and inducible STAT3 activation at tyrosine residue 705 but not at serine residue 727 in human multiple myeloma cells. Besides the inhibition of STAT3 phosphorylation, CPS also abrogated STAT3 constitutive activity and nuclear translocation. The suppression of STAT3 was mediated through the inhibition of activation of upstream JAK1, JAK2, and c-Src kinases. Treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate treatment reversed the CPS-induced down-regulation of JAK1/2 and STAT3, thereby suggesting the involvement of a PTP. Indeed, knockdown of the SHP-1 and SHP-2 genes by small interfering RNA suppressed the ability of CPS to inhibit JAK1 and STAT3 activation, suggesting the critical role of both SHP-1 and SHP-2 in its p...Continue Reading

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Citations

May 20, 2015·Immunopharmacology and Immunotoxicology·Seung Ho BaekKwang Seok Ahn
Oct 29, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Moon Kyung JooYoung-Tae Bak
Jun 9, 2017·International Journal of Molecular Sciences·Tzu-Ting HuangKuen-Feng Chen
Oct 1, 2020·Biomolecules·Ebrahim Rahmani MoghadamAlan Prem Kumar
May 25, 2016·World Journal of Gastroenterology : WJG·Moon Kyung JooHoon Jai Chun
Sep 12, 2018·Cell & Bioscience·Jin Sung KohSang Woo Lee
Dec 9, 2020·Cancer Letters·Pegah AbdollahiMagne Børset
Dec 18, 2020·Life Sciences·Semim Akhtar AhmedAjaikumar B Kunnumakkara
Apr 24, 2020·Seminars in Cancer Biology·Chakrabhavi Dhananjaya MohanKanchugarakoppal S Rangappa
Nov 11, 2020·International Journal of Molecular Sciences·Min Hee YangKwang Seok Ahn
Jun 2, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Chakrabhavi Dhananjaya MohanKanchugarakoppal S Rangappa
May 20, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Young Yun JungKwang Seok Ahn

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