Camptothecin and topotecan inhibit adipocyte differentiation by inducing degradation of PPARγ

Jung Hoon Kim, Manhyung Jeong, Sang Sik Lee, Jaewhan Song

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1122-1128
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume463
Issue number4
DOIs
Publication statusPublished - 2015 Jul 13

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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