An anti-prostate cancer benzofuran-conjugated iridium(III) complex as a dual inhibitor of STAT3 and NF-κB.
Four benzofuran-conjugated iridium(III) or rhodium (III)-based metal complexes are synthesized to screen as an inhibitor of STAT3 activity in prostate cancer cells. All complexes show the high stability and solubility in the biological system. In this study, an iridium(III) complex engages STAT3 and NF-κB to inhibit their translocation and transcriptional activities. Moreover, complex 1 shows more potential antiproliferative activity against DU145 cells and suppresses tumor growth in a prostate cancer xenograft mouse without observable adverse effects. Complex 1 may provide the basis for developing new therapeutic strategy in vivo and in vitro for the treatment of advanced prostate cancer.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Tian-Shu
TS
Kang
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Wanhe
W
Wang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Hai-Jing
HJ
Zhong
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Zhen-Zhen
ZZ
Dong
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China.
Qi
Q
Huang
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China.
Simon Wing Fai
SW
Mok
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: duncanleung@umac.mo.
Chung-Hang
CH
Leung
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China. Electronic address: kawwong@must.edu.mo.
Vincent Kam Wai
VK
Wong
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address: edmondma@hkbu.edu.hk.
Dik-Lung
DL
Ma
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011897:Random Allocation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D001572:Benzofurans; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007495:Iridium; C105430:benzofuran
Benzofuran-conjugated iridium(III) complex; Dual inhibitors; NF-κB; Prostate cells; STAT3