Camptothecin and topotecan inhibit adipocyte differentiation by inducing degradation of PPARγ

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

doi:10.1016/j.bbrc.2015.06.069

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 journal › Article › peer-review

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 language	English
Pages (from-to)	1122-1128
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	463
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2015.06.069
Publication status	Published - 2015 Jul 13

Bibliographical note

Funding Information:
This study was supported by the National Cancer Center , Korea ( NCC-1420300 ), and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health & Welfare of the Republic of Korea ( HI12C1280 ).

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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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.",

author = "Kim, {Jung Hoon} and Manhyung Jeong and Lee, {Sang Sik} and Jaewhan Song",

note = "Funding Information: This study was supported by the National Cancer Center , Korea ( NCC-1420300 ), and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health & Welfare of the Republic of Korea ( HI12C1280 ). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc. All rights reserved.",

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doi = "10.1016/j.bbrc.2015.06.069",

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AU - Lee, Sang Sik

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N1 - Funding Information: This study was supported by the National Cancer Center , Korea ( NCC-1420300 ), and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health & Welfare of the Republic of Korea ( HI12C1280 ). Publisher Copyright: © 2015 Elsevier Inc. All rights reserved.

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Y1 - 2015/7/13

N2 - 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.

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Camptothecin and topotecan inhibit adipocyte differentiation by inducing degradation of PPARγ

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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