Effects of celastrol on enhancing apoptosis of ovarian cancer cells via the downregulation of microRNA-21 and the suppression of the PI3K/Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma

Abstract

Abstract. Celastrol has previously been used to treat rheumatoid arthritis, bruises, back pain and additional diseases. At present, efficacy studies predominantly focus on the anti-inflammatory, antioxidative and antitumor effects of celastrol. However, the effect of celastrol on ovarian cancer cells is not fully elucidated. In the present study, the effects of celastrol were investigated in ovarian cancer cells and the mechanisms involved were explored. In OVCAR3 cells, celastrol was observed to suppress cellular proliferation, induce apoptosis and increase caspase-9 and -3 activity in a dose-and time-dependent manner. The expression levels of microRNA-21 (miRNA-21) were reduced, in addition to a reduction in the levels of phosphoinositide 3-kinase (PI3K)/p-Akt-NF (NF)-κB following treatment with celastrol. Notably, reduced expression of miRNA-21 replicated the effect of celastrol on OVCAR3 cells and inhibited the PI3K/p-Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma. To the best of our knowledge this is the first study to indicate that celastrol may represent a potential agent for the treatment of human ovarian carcinoma, via the induction of apoptosis through the downregulation of miRNA-21 and the PI3K/Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma.

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

“…In fact, some scholars reported that down-regulation of miR-21 inhibited PI3K/Akt-NF-κB signaling pathway and promoted apoptosis in OVCAR3 cells. 51 This was consistent with our study that HUMSC-Exos underexpressed miR-21a-3p, synchronizing with p65 inactivation and inhibited cell viability in fibroblasts. In contrast, some scholars found that after treatment with miR-21 mimic-loaded human peripheral blood-derived exosomes, gene expression levels of mothers against decapentaplegic homolog 3 (Smad7), phosphatase and tension homologue (PTEN) and matrix metalloproteinase 2 (MMP2) associated with cardiac fibrosis increased both in vivo and in vitro.…”

Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo

“…In our present study, we have demonstrated that celastrol mediated dose-dependent anti-growth effects on human ovarian cancer cell lines SKOV3 and A2780. The IC 50 value after 72 h treatment with celastrol ranged from 2 to 3 μM in these two human ovarian cancer cell lines, similarly to the IC 50 value of celastrol of ovarian cancer in other articles (15, 16). We have also shown that celastrol induced both the early and late stage of apoptosis and cell cycle arrest in G2/M phase with obvious up-regulation of cleaved-PARP, pp38 T180/Y182, pJNK T183/Y185, p27 and Cyclin B1 and down-regulation of pERK T202/Y204, pAKT S473, RAF1 and Cyclin E in a dose-dependent manner.…”

“…For the treatment of ovarian cancer, triptolide has been shown to inhibit the proliferation, migration and invasion of ovarian cancer in multiple pathways (29–31) and demonstrated to exert efficacy in preclinical models (32). Celastrol has also been reported to induce apoptosis and inhibit proliferation, migration and invasion in ovarian cancer cells in vitro (14, 16), but the mechanism for its anti-tumor effect and the effect of celastrol on the growth of ovarian cancer cells in vivo are not fully understood. In our present study, we have demonstrated that celastrol mediated dose-dependent anti-growth effects on human ovarian cancer cell lines SKOV3 and A2780.…”

“…Celastrol has shown the potent antitumor activity in various cancers including prostate, breast, liver, colon, and lung (9–13). Although celastrol is able to induce apoptosis and inhibit proliferation, migration and invasion in ovarian cancer cells in vitro (14–16), the effect of celastrol on the growth of ovarian cancer cells in vivo is still unknown. Here, we have comprehensively investigated the antitumor activity of celastrol in ovarian cancer cells in vitro and in vivo .…”

Celastrol Suppresses Tryptophan Catabolism in Human Colon Cancer Cells as Revealed by Metabolic Profiling and Targeted Metabolite Analysis

“…Currently, a few molecules or signal pathways were reported to be involved in the anti-cancer mechanisms of celastrol. [4][5][6] For example, celastrol down-regulated phosphatidylinositol 3-kinase (PI3K)/Akt/ nuclear factor-kappaB (NF-κB) signaling pathway in osteosarcoma and ovarian cancer cells 7,8) ; celastrol was reported to suppress the invasion and metastasis of colon cancer cells through down-regulating the expression of CXCR4 chemokine receptor, 9) yet other mechanisms of celastrol against colon cancer are still not fully elucidated.…”