Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins

Abstract

Abstract:Background: Recent studies have shown that anisomycin significantly inhibits mammalian cell proliferation, but its mechanism remains unclear. In this study, Jurkat T cells were used to first explore a relationship between effect of anisomycin on them and alteration of cell cycle-regulating proteins. Methods: Cell colony formation, CCK-8 assay, flow cytometry, RT-PCR and western blot were employed to evaluate correlation of ten cell cycle-regulating proteins with suppression of the cell proliferation and arrest of the cell cycle by anisomycin. Results: Our data showed that anisomycin inhibited the colony-formation and proliferation of Jurkat T cells in a dose-dependent manner, and arrested the cells into S and G2/M phases with the production of sub-diploid cells. The levels of P21, P-P27 and P53/P-P53 reached their peaks 4 h after anisomycin treatment, presenting a positive correlation with anisomycin concentration, and P16, P-P21, P27, P57, P73/P-P73 and P-Rb changed little with the prolonged exposure time or increased concentrations of anisomycin. But the level of Rb protein was increased at 24 h after the treatment of anisomycin. The expression of an inverted CCAAT box binding protein (ICBP90) in Jurkat T cells came to decrease 12 h after the treatment of anisomycin, presenting a negative correlation with anisomycin concentration. Subsequently, the expression of P-CDK2 was also decreased at 24 h, presenting an obviously negative correlation, whereas P-CDK1 showed no differences among the differently treated Jurkat T cells. Furthermore, the level of P21 and P53 mRNA was increased with the enhanced concentrations of anisomycin. Conclusion:The results indicate that anisomycin may activate the P53/P21/P27 signaling to decrease the expression of ICBP90, inhibit expression of P-CDK2 to block the cells into S and G2/M phases, and finally result in proliferation inhibition of Jurkat T cells.

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

“…Since cancer stem cells are resistant to most traditional chemotherapeutic drugs, such as cisplatin and paclitaxel, it is necessary to develop more effective drugs for tumour chemotherapy (21,(29)(30)(31). Anisomycin has been confirmed to have significant inhibitory effects on a variety of solid tumours and is a promising chemotherapeutic drug candidate (7)(8)(9)(10)(11). Our previous report has revealed that anisomycin inhibits the proliferation and invasion of ovarian cancer stem cells by enhancing the activity of lncRNA-BACE1-AS and increasing the release of endogenous Aβ42 (7).…”

“…The present study suggested that anisomycin may have the potential to inhibit cancer stem cells. Based on the existing reports (7)(8)(9)(10)(11), it was speculated that the inhibitory effect of anisomycin on cancer stem cells may depend on multi-target regulation. Therefore, it is meaningful to explore its in-depth mechanism.…”

“…Previous studies have shown that anisomycin can promote the production of amyloid β (Aβ) 1-42 causing neurotoxicity, as well as inhibit the proliferation of certain cancer cells. Yu et al (9) found that anisomycin inhibited the proliferation of Jurkat T cells by promoting the expression of p53, p21 and p27, thus stopping the cells from entering the S and G2/M phases. Seo et al (10) reported that anisomycin could induce apoptosis in renal tumour cells by downregulating Bcl-2, c-FLIPL and Mcl-1.…”

Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer

“…5), have been also reported to efficiently affect UHRF1 expression [111, 112]. Nevertheless, the mechanism of UHRF1 downregulation induced by natural compounds that target the signaling pathways of UHRF1 expression remains to be deciphered, but might involve the proteasome pathway.…”

Long non-coding RNA BACE1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion

“…A recent study showed that inhibition of microRNA-20a expression increases APP expression and suppresses ovarian cancer cell proliferation and invasion (10). Similarly, other studies indicate that anisomycin, a small molecule antibiotic, can inhibit the proliferative and invasive ability of some tumor cells by increasing the production of the toxic amyloid β (Aβ1-42) peptides from APP (11,(15)(16)(17)(18)(19). In particular, anisomycin [2-(p-methoxybenzyl)-3,4-pyrrolidinediol-3-acetate] increases mRNA expression of APP, β-site APP cleaving enzyme 1 (BACE1 or β-secretase) and presenilin 1 (PS1) in a human SH-SY5Y cell line (10).…”