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

Abstract

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.

Icariin‑curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO‑1 signaling

“…Icariin can promote ferroptosis of tumor cells by interfering with ferroptosis metabolism pathways ( 26 ). Specifically, it can inhibit uptake of ferroptosis in tumor cells and disrupt the balance of ferroptosis storage and utilization, leading to ferroptosis overload in tumor cells.…”

“…icariin and curcumol can inhibit tumor growth by suppressing the proliferation of tumor cells. Additionally, both icariin and curcumol have anti-inflammatory effects ( 26 ). Inflammation is an important factor in the occurrence and development of tumors and by inhibiting the occurrence of inflammatory reactions, tumor growth and spread can be suppressed ( 27 ).…”

“…Icariin and curcumol both have pharmacological activities and by mixing them together, they may produce a synergistic effect, enhancing the therapeutic effect ( 27 ). Previous experiments have demonstrated that Icariin and curcumin synergistically regulate the miR-7/mTOR/SREBP1 pathway, inducing autophagy and ferroptosis in PCa cells and affecting lipid metabolism ( 26 ). DU145 cells may have differences in the regulation of the Nrf2/HO-1 signaling pathway compared with other PCa cells such as RWPE-2, PC-3 and VCAP.…”

“…The present authors' initial study indicated that curcumol effectively inhibits the proliferation, invasion and migration of PC3 and 22RV1 cells, mitigating the progression of PCa via the miR-125a/STAT3 axis ( 25 ). Icariin and curcumol act synergistically to modulate the miR-7/mTOR/SREBP1 pathway, inducing autophagy in PCa cells and affecting lipid metabolism ( 26 ). Our latest experiments suggested that icariin and curcumol increase Fe 2+ and malondialdehyde (MDA) contents while decreasing GSH levels, whereas treatment with Fer-1, an iron death inhibitor, reversed these indexes ( 26 ).…”

“…Icariin and curcumol act synergistically to modulate the miR-7/mTOR/SREBP1 pathway, inducing autophagy in PCa cells and affecting lipid metabolism ( 26 ). Our latest experiments suggested that icariin and curcumol increase Fe 2+ and malondialdehyde (MDA) contents while decreasing GSH levels, whereas treatment with Fer-1, an iron death inhibitor, reversed these indexes ( 26 ). However, it remains to be seen whether icariin-curcumol interferes with PCa progression by promoting ferroptosis of PCa cells.…”