Janerin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis Involving the MAPK Pathway in THP-1, Leukemic Cell Line

Abstract

Janerin is a cytotoxic sesquiterpene lactone that has been isolated and characterized from different species of the Centaurea genus. In this study, janerin was isolated form Centaurothamnus maximus, and its cytotoxic molecular mechanism was studied in THP-1 human leukemic cells. Janerin inhibited the proliferation of THP-1 cells in a dose-dependent manner. Janerin caused the cell cycle arrest at the G2/M phase by decreasing the CDK1/Cyclin-B complex. Subsequently, we found that janerin promoted THP-1 cell death through apoptosis as indicated by flow cytometry. Moreover, apoptosis induction was confirmed by the upregulation of Bax, cleaved PARP-1, and cleaved caspase 3 and the downregulation of an anti-apoptotic Bcl-2 biomarker. In addition, immunoblotting indicated a dose dependent upregulation of P38-MAPK and ERK1/2 phosphorylation during janerin treatment. In conclusion, we have demonstrated for the first time that janerin may be capable of inducing cell cycle arrest and apoptosis through the MAPK pathway, which would be one of the mechanisms underlying its anticancer activity. As a result, janerin has the potential to be used as a therapeutic agent for leukemia.

Assessment of the Anticancer Effect of Chlorojanerin Isolated from Centaurothamnus maximus on A549 Lung Cancer Cells

“…Our annexin V/PI staining experiment demonstrated that apoptosis is the primary mechanism involved in chlorojanerin-mediated cell death. In our previous study [ 21 ], the THP-1 leukemic cell line also showed similar apoptotic patterns following janerin treatment.…”

“…In this study, we show that chlorojanerin caused an accumulation of cells in the G2/M phase after 24 h of treatment. The scenario described here for the induction of G2/M phase cell cycle arrest in suppressing the proliferation of A549 cells has been demonstrated in our previous work with janerin compound that induced G2/M phase cell cycle arrest in human leukemia cancer cells [ 21 ].…”

“…Among natural plant products, sesquiterpene lactones still represent an interesting source of therapeutic bioactive compounds that exhibit cytotoxic properties [ 19 , 20 ]. In our exploration of anticancer agents from C. maximus, we have previously reported that janerin, a sesquiterpene lactone, exhibited growth inhibitory effects against leukemia cancer cells [ 21 ]. In the current study, we isolated another sesquiterpene lactone from C. maximus and assessed its cytotoxic potential and the underlying mechanism.…”

Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo

“…The expression of Cyclin B and cdc2 was significantly decreased, but the expression of p-p53 and p21 upstream of them was remarkably increased ( Figure 3 C,D). The above results show that isorhamnetin can inhibit the proliferation of Ishikawa cells in the G2/M phase [ 30 ].…”

“…The expression of Cyclin B and cdc2 was significantly decreased, but the expression of p-p53 and p21 upstream of them was remarkably increased (Figure 3C,D). The above results show that isorhamnetin can inhibit the proliferation of Ishikawa cells in the G2/M phase [30]. In order to further investigate the mechanism of the cell cycle influenced by isorhamnetin, we investigated protein expression levels.…”