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Morusinol Extracted from Morus alba Inhibits Cell Proliferation and Induces Autophagy via FOXO3a Nuclear Accumulation-Mediated Cholesterol Biosynthesis Obstruction in Colorectal Cancer.
Zhang, Xiaolin; Dong, Zhen; Yang, Yuanmiao; Liu, Chaolong; Li, Jisheng; Sun, Wenli; Zhu, Yikang; Shen, Yang; Wang, Zhi; Lü, Muhan; Cui, Hongjuan.
Afiliação
  • Zhang X; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Dong Z; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Yang Y; Jinfeng Laboratory, Chongqing 401329, China.
  • Liu C; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing 400716, China.
  • Li J; Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing 400716, China.
  • Sun W; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Zhu Y; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Shen Y; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Wang Z; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Lü M; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • Cui H; State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China.
J Agric Food Chem ; 71(43): 16016-16031, 2023 Nov 01.
Article em En | MEDLINE | ID: mdl-37870273
The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Morus / Antineoplásicos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Morus / Antineoplásicos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article