TY - JOUR
T1 - Therapeutic suppression of constitutive and inducible JAK\STAT activation in head and neck squamous cell carcinoma
AU - Kupferman, Michael E.
AU - Jayakumar, Arumugam
AU - Zhou, Ge
AU - Xie, Tong
AU - Dakak-Yazici, Yasemin
AU - Zhao, Mei
AU - Ju, Jun
AU - Mandal, Mahitosh
AU - Jasser, Samar
AU - Madden, Timothy
AU - Myers, Jeffrey N.
AU - Priebe, Waldemar
PY - 2009
Y1 - 2009
N2 - The oncogenic role of STAT3 has been elucidated in a number of human malignancies including leukemia, lymphoma, malignant glioma and cancers of the breast, lung, and head and neck (HNSCC). Here we show that WP1066 has profound anti-neoplastic effects in HNSCC, mediated in part by suppression of JAK2-STAT3 signaling. WP1066 inhibited constitutive and inducible STAT3 phosphorylation in both dose- and time-dependant manners. Further, the nuclear translocation of STAT3 was completely inhibited, resulting in decreased DNA binding activity. In vivo testing of WP1066 in a nude mouse orthotopic model of HNSCC demonstrated significant anti-tumor effects, with histological evidence of decreased cellular proliferation and angiogenesis. Collectively, these data suggest that WP1066 suppresses squamous cell carcinoma cell growth, in part through its effects on JAK-STAT pathways, and establishes this small molecule as potentially efficacious agent in the treatment of HNSCC.
AB - The oncogenic role of STAT3 has been elucidated in a number of human malignancies including leukemia, lymphoma, malignant glioma and cancers of the breast, lung, and head and neck (HNSCC). Here we show that WP1066 has profound anti-neoplastic effects in HNSCC, mediated in part by suppression of JAK2-STAT3 signaling. WP1066 inhibited constitutive and inducible STAT3 phosphorylation in both dose- and time-dependant manners. Further, the nuclear translocation of STAT3 was completely inhibited, resulting in decreased DNA binding activity. In vivo testing of WP1066 in a nude mouse orthotopic model of HNSCC demonstrated significant anti-tumor effects, with histological evidence of decreased cellular proliferation and angiogenesis. Collectively, these data suggest that WP1066 suppresses squamous cell carcinoma cell growth, in part through its effects on JAK-STAT pathways, and establishes this small molecule as potentially efficacious agent in the treatment of HNSCC.
KW - JAK\STAT
KW - Small molecule
KW - Squamous cell carcinoma
KW - Targeted inhibition
UR - http://www.scopus.com/inward/record.url?scp=74249116204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74249116204&partnerID=8YFLogxK
M3 - Article
C2 - 20192118
AN - SCOPUS:74249116204
SN - 1359-4117
VL - 8
SP - 117
EP - 127
JO - Journal of Experimental Therapeutics and Oncology
JF - Journal of Experimental Therapeutics and Oncology
IS - 2
ER -