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

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.

Combined therapy of ruthenium dendrimers and anti-cancer drugs against human leukemic cells

Carbosilane ruthenium(II) dendrimers have been complexed with conventional anti-cancer drugs. Due to its features, the presence of ruthenium within a dendrimer structure improves the anti-cancer properties of nanocomplexes containing 5-flurouracyl,...

New prodrugs and analogs of the phenazine 5,10-dioxide natural products iodinin and myxin promote selective cytotoxicity towards human acute myeloid leukemia cells

Synthetic derivatives of the phenazine 5,10-dioxide natural antibiotics iodinin and myxin were shown to be potent and selective towards human leukemic cells.

Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.