FIGURE 3.

The molecular mechanisms of celastrol in liver cancer (edited by Biorender software). Celastrol exert anticancer effect by restraining their cell growth, metastasis, and inflammatory response, while boosting ER stress, apoptosis, and autophagy depending on modulated different signaling pathways. Firstly, celastrol can activate cancer cell apoptosis through inhibiting JAK2 and STAT3 phosphorylation, then downregulated BCL-2 family proteins (Bcl-2 and Bcl-xl) and upregulated caspase family proteins (caspase 3 and caspase 9). Secondly, celastrol repressed tumor cell proliferation by suppressing cyclin D1 and c-myc through E2F1 and STAT3; Lastly, celastrol prohibited tumor metastasis by NF-κB signaling pathway modulated MMP-2 and MMP-9 through the CXCR4-related signaling pathway, as well as the ROCK2-mediated phosphorylation of ezrin at Thr567. ER, endoplasmic reticulum; JAK1, Janus kinase1; JAK2, Janus kinase2; STAT3, signal transducer and activator of transcription 3; Bcl-2, B-cell lymphoma-2; PI3K, phosphatidylinositol-3-kinase; AKT, protein kinase B; NF-kB, nuclear factor kappa B; MMP2, Matrix metallopeptidase 2; MMP9, Matrix metallopeptidase 9; circ_SLIT3, circRNA slit guidance ligand 3; ROCK2, Rho Associated Coiled-Coil Containing Protein kinase 2.