title: Tyrosine kinase inhibitor AG490 inhibits the proliferation and migration and disrupts actin organization of cancer cells.
abstract: Metastasis, a multistep process, is a major cause of mortality in cancer patients. Thus, it is hoped that inhibition of metastasis at any step, such as proliferation, migration, or invasion, using small-molecule inhibitors will reduce this mortality. Recent study suggests that the Janus kinase/signal transducer and activator of transcription 3 signal transduction pathway is a central pathway that regulates tumor progression and metastasis and can be blocked using tyrosine kinase inhibitors. In this study we used a synthetic tyrosine kinase inhibitor, AG490, to block the constitutive activation of the Janus kinase/signal transducer and activator of transcription 3 pathway in A549 lung carcinoma and A375 melanoma cell lines. Our results show that AG490 at subtoxic doses can effectively suppress tumor cell proliferation by limiting the expression of cyclin D1. Furthermore, AG490 is seen to induce apoptosis, inhibit cellular migration by disrupting actin organization, and suppress matrix metalloproteinase 2 activity. Taken together, these data demonstrate that AG490 can exert antimetastatic activity by inhibiting cellular proliferation, invasion, and migration.
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Mohammad Zahid
authors.initials: MZ
authors.lastname: Kamran
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Patil
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Shirsath
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Rajiv P
authors.initials: RP
authors.lastname: Gude
mesh_terms: D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D019938:Cyclin D1; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D020778:Matrix Metalloproteinase 2