Artificial Water Channel Promoting Depolymerization of Actin Filaments to Trigger Cancer Cell Apoptosis
Lei Zhang
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorYin-Gui Cao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences Institution, Southwest University, Chongqing, 400715 China
Search for more papers by this authorTing Fan
ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, 200031
Search for more papers by this authorJiatong Zhao
Fudan International School, 325 Guoquan Road, Shanghai, 200433 China
Search for more papers by this authorYong-Hong Fu
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorQi Xiao
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorZhan-Ting Li
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorCorresponding Author
Yunfeng Wang
ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, 200031
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorCorresponding Author
Bo Xiao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences Institution, Southwest University, Chongqing, 400715 China
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorCorresponding Author
Jun-Li Hou
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorLei Zhang
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorYin-Gui Cao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences Institution, Southwest University, Chongqing, 400715 China
Search for more papers by this authorTing Fan
ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, 200031
Search for more papers by this authorJiatong Zhao
Fudan International School, 325 Guoquan Road, Shanghai, 200433 China
Search for more papers by this authorYong-Hong Fu
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorQi Xiao
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorZhan-Ting Li
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
Search for more papers by this authorCorresponding Author
Yunfeng Wang
ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, 200031
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorCorresponding Author
Bo Xiao
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences Institution, Southwest University, Chongqing, 400715 China
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorCorresponding Author
Jun-Li Hou
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433 China
E-mail: [email protected], [email protected], [email protected]Search for more papers by this authorComprehensive Summary
Actin filaments play important physiological functions, which have become potential targets of antitumor drugs. Using chemicals to intervene their polymerization-depolymerization dynamics would generate new strategies for designing antitumor drugs. In this report, an artificial water channel appending acetazolamide moiety, a ligand that can selectively bind to carbonic anhydrase IX, has been prepared. We demonstrated that this conjugate can target colorectal cancer cells overexpressing carbonic anhydrase IX and trigger the depolymerization of actin filaments of the cancer cells by selectively mediating water transmembrane transport. Moreover, the conjugate-promoted actin depolymerization led to tumor cell apoptosis and its high antitumor activity in vitro and in vivo against colorectal cancer. The method described herein represents a new and general strategy for designing antitumor drugs by using artificial channel-mediated selective water transport to promote actin depolymerization.
Supporting Information
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Appendix S1: Supporting Information |
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