Effects of icariin and curcumol on autophagy, ferroptosis, and lipid metabolism based on miR-7/m-TOR/SREBP1 pathway on prostate cancer

被引:18
|
作者
Xu, Wenjing [1 ]
Ding, Jin [2 ]
Li, Bonan [3 ,4 ]
Sun, Tiansong [3 ,4 ]
You, Xujun [2 ]
He, Qinghu [3 ,5 ,7 ]
Sheng, Wen [3 ,6 ,7 ]
机构
[1] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Dermatol, Changsha, Peoples R China
[2] Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Androl, Shenzhen, Peoples R China
[3] Hunan Univ Chinese Med, Androl Lab, Changsha, Peoples R China
[4] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Changsha, Peoples R China
[5] Hunan Univ Med, Coll Tradit Chinese Med, Huaihua, Peoples R China
[6] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China
[7] Hunan Univ Chinese Med, Androl Lab, 300 Xueshi Rd, Changsha 410208, Peoples R China
关键词
autophagy; curcumol; ferroptosis; ICA; prostate cancer; CELL; APOPTOSIS; GROWTH; MIR-7; PROGRESSION;
D O I
10.1002/biof.1927
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study aimed to investigate the effects and underlying molecular mechanisms of icariin (ICA) and curcumol on autophagy, ferroptosis, and lipid metabolism in prostate cancer (PCa), in vitro and in vivo. Normal prostate epithelial cells RWPE-1 and PCa cell lines DU145 and PC-3 were treated with ICA and curcumol. Ferrostatin-1 (Fer-1) or 3-MA was added to treat DU145 and PC-3 cells. In addition, we knocked down miR-7. The mechanism of ICA and curcumol in PCa cells after the knockdown of miR-7 was verified by in vitro nude mice tumorigenesis experiments. ICA and curcumol had no significant effect on the viability of RWPE-1 cells, but there was a significant difference between DU145 and PC-3 cells. After treatment with ICA and curcumol, the proliferation of PCa cells was inhibited, apoptosis, reactive oxygen species (ROS) levels, and miR-7 expression were increased. The combined treatment of ICA and curcumol had a more significant effect. ICA and curcumol treatment induced autophagy and ferroptosis in PCa cells, and si-miR-7 reversed the effects of ICA and curcumol on autophagy and ferroptosis. MiR-7 targeted mTOR and regulated the expression of the mTOR/SREBP1 pathway in PCa cells. ICA and curcumol may affect the lipid metabolism of PCa cells by affecting SREBP1. In addition, the effects and mechanisms of ICA and curcumol on autophagy, ferroptosis, and lipid metabolism in PCa cells were verified in vivo. ICA and curcumol synergistically regulated the miR-7/mTOR/SREBP1 pathway to induce autophagy and ferroptosis in PCa cells and affected lipid metabolism.
引用
收藏
页码:438 / 456
页数:19
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