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.
Highlights
Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy marked by the abnormal clonal expansion of myeloid blast cells in bone marrow and peripheral blood
Our findings clearly demonstrated that the janerin janerin arrested the THP-1 cells at the G2/M phase and induced apoptosis through the arrested the THP-1 cells at the G2/M phase and induced apoptosis through the activation activation of the MAPK pathway
We found that janerin significantly reduced cyclin B1 and CDK-1 levels in a dose-dependent manner (Figure 4), confirming that the lowering of these proteins caused a cell cycle arrest at the G2/M phase
Summary
Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy marked by the abnormal clonal expansion of myeloid blast cells in bone marrow and peripheral blood. Different therapies have been employed for AML including radiation therapy and chemotherapy [2]. The current understanding of AML pathophysiology has resulted in the approval of several medicines for various symptoms of AML [3]. All these choices still cause numerous side effects in a broad range of body cells [4]. Natural products from medicinal plants represent an alternative choice with minimum side effects
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