RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression
Lipogenesis plays a critical role in the growth and metastasis of tumors, which is becoming an attractive target for anti-tumor drugs. RA-XII, one of the cyclopeptide glycosides isolated from <i>Rubia yunnanensis</i>, exerts anti-tumor effects on liver cancer. However, the underlying mec...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-05-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/24/9/1829 |
id |
doaj-87bd3bfa3bf24c64b9f6f14450a0f964 |
---|---|
record_format |
Article |
spelling |
doaj-87bd3bfa3bf24c64b9f6f14450a0f9642020-11-24T21:45:16ZengMDPI AGMolecules1420-30492019-05-01249182910.3390/molecules24091829molecules24091829RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP SupressionDi Guo0Yurong Wang1Jing Wang2Lihua Song3Zhe Wang4Bingyu Mao5Ninghua Tan6State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaState Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaState Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaState Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaState Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223 Kunming, ChinaState Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 211198 Nanjing, ChinaLipogenesis plays a critical role in the growth and metastasis of tumors, which is becoming an attractive target for anti-tumor drugs. RA-XII, one of the cyclopeptide glycosides isolated from <i>Rubia yunnanensis</i>, exerts anti-tumor effects on liver cancer. However, the underlying mechanisms are not clear. In the present study, the effects of RA-XII on lipogenesis were evaluated and the underlying mechanisms were investigated. The results indicated that RA-XII strongly inhibited tumor growth and lipogenesis (triglycerides and lipid droplets) in HepG2 cells, and the expression of key factors involved in lipogenesis (SREBP, SCD, FASN) was also obviously downregulated. Further investigation showed that the anti-tumor effects of RA-XII were attenuated by SREBP knockdown. Moreover, RA-XII downregulated the expression of SREBP cleavage-activating protein (SCAP), an upstream regulator of SREBP, and siRNA of SCAP prevented its restrained effects on tumor growth and lipogenesis. In addition, the in vivo experiment showed that RA-XII strongly restrained the lipogenesis and growth of liver tumor in nude mice xenograft model. Taken together, these results indicate that RA-XII suppresses the liver cancer growth by inhibition of lipogenesis via SCAP-dependent SREBP suppression. The findings reveal the potentials of RA-XII to be used in a novel therapeutic approach for treating liver cancer.https://www.mdpi.com/1420-3049/24/9/1829RA-XIIlipogenesisSCAPSREBPliver cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Di Guo Yurong Wang Jing Wang Lihua Song Zhe Wang Bingyu Mao Ninghua Tan |
spellingShingle |
Di Guo Yurong Wang Jing Wang Lihua Song Zhe Wang Bingyu Mao Ninghua Tan RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression Molecules RA-XII lipogenesis SCAP SREBP liver cancer |
author_facet |
Di Guo Yurong Wang Jing Wang Lihua Song Zhe Wang Bingyu Mao Ninghua Tan |
author_sort |
Di Guo |
title |
RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression |
title_short |
RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression |
title_full |
RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression |
title_fullStr |
RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression |
title_full_unstemmed |
RA-XII Suppresses the Development and Growth of Liver Cancer by Inhibition of Lipogenesis via SCAP-dependent SREBP Supression |
title_sort |
ra-xii suppresses the development and growth of liver cancer by inhibition of lipogenesis via scap-dependent srebp supression |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-05-01 |
description |
Lipogenesis plays a critical role in the growth and metastasis of tumors, which is becoming an attractive target for anti-tumor drugs. RA-XII, one of the cyclopeptide glycosides isolated from <i>Rubia yunnanensis</i>, exerts anti-tumor effects on liver cancer. However, the underlying mechanisms are not clear. In the present study, the effects of RA-XII on lipogenesis were evaluated and the underlying mechanisms were investigated. The results indicated that RA-XII strongly inhibited tumor growth and lipogenesis (triglycerides and lipid droplets) in HepG2 cells, and the expression of key factors involved in lipogenesis (SREBP, SCD, FASN) was also obviously downregulated. Further investigation showed that the anti-tumor effects of RA-XII were attenuated by SREBP knockdown. Moreover, RA-XII downregulated the expression of SREBP cleavage-activating protein (SCAP), an upstream regulator of SREBP, and siRNA of SCAP prevented its restrained effects on tumor growth and lipogenesis. In addition, the in vivo experiment showed that RA-XII strongly restrained the lipogenesis and growth of liver tumor in nude mice xenograft model. Taken together, these results indicate that RA-XII suppresses the liver cancer growth by inhibition of lipogenesis via SCAP-dependent SREBP suppression. The findings reveal the potentials of RA-XII to be used in a novel therapeutic approach for treating liver cancer. |
topic |
RA-XII lipogenesis SCAP SREBP liver cancer |
url |
https://www.mdpi.com/1420-3049/24/9/1829 |
work_keys_str_mv |
AT diguo raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT yurongwang raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT jingwang raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT lihuasong raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT zhewang raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT bingyumao raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression AT ninghuatan raxiisuppressesthedevelopmentandgrowthoflivercancerbyinhibitionoflipogenesisviascapdependentsrebpsupression |
_version_ |
1725905485781008384 |