title: Camptothecin and topotecan inhibit adipocyte differentiation by inducing degradation of PPARγ.
abstract: Camptothecin is an anti-cancer drug extracted from Camptotheca acuminata, a tree native to mainland China. Phase III clinical trials for camptothecin have been completed, and it is now used as a chemotherapeutic reagent. We identified a novel function of camptothecin that affects adipocyte differentiation. Following treatment with camptothecin, endogenous or overexpressed PPARγ becomes destabilized; this was prevented in the presence of MG132, a proteasome inhibitor. Our findings suggest that camptothecin is able to induce proteasome-dependent degradation of PPARγ. The ubiquitylation of PPARγ increased in the presence of camptothecin. Adipogenic differentiation of 3T3-L1 cells was prevented by campothecin and topotecan, but not by irinotecan, confirming our initial findings. Our results suggest a possible role for camptothecin analogs in the regulation of PPARγ.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Manhyung
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Engineering, Catholic Kwandong University, Gangneung, Republic of Korea.
authors.forename: Sang-sik
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. Electronic address: jso678@yonsei.ac.kr.
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002166:Camptothecin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D059748:Proteolysis; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*; D019772:Topotecan / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D002166:Camptothecin
keywords: Adipocyte differentiation; Camptothecin; PPARγ; Topotecan