Calycosin inhibits the proliferation and metastasis of renal cell carcinoma through the MAZ/HAS2 signaling pathway.

Autor:	Zhang ZH; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.; Department of Urology, School of Life Medicine, Fudan University Shanghai Cancer Center, Qingdao Institute, Fudan University, Qingdao, China., Yuan CY; Central Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Xu M; Central Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Wang MF; Central Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Feng T; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.; Department of Urology, School of Life Medicine, Fudan University Shanghai Cancer Center, Qingdao Institute, Fudan University, Qingdao, China., Wang Y; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Zheng SF; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.; Department of Urology, School of Life Medicine, Fudan University Shanghai Cancer Center, Qingdao Institute, Fudan University, Qingdao, China., Zhang HL; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Shi GH; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Cao DL; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Wang ZL; Central Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Ye DW; Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.; Shanghai Genitourinary Cancer Institute, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.; Department of Urology, School of Life Medicine, Fudan University Shanghai Cancer Center, Qingdao Institute, Fudan University, Qingdao, China.
Jazyk:	angličtina
Zdroj:	Phytotherapy research : PTR [Phytother Res] 2024 Sep; Vol. 38 (9), pp. 4774-4791. Date of Electronic Publication: 2024 Aug 09.
DOI:	10.1002/ptr.8295
Abstrakt:	Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma. (© 2024 John Wiley & Sons, Ltd.)
Databáze:	MEDLINE
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