Pinostrobin, a fingerroot compound, regulates miR-181b-5p and induces acute leukemic cell apoptosis.

Pinostrobin (PN) is the most abundant flavonoid found in fingerroot. Although the anti-leukemic properties of PN have been reported, its mechanisms are still unclear. MicroRNAs (miRNAs) are small RNA molecules that function in posttranscriptional silencing and are increasingly being used in cancer therapy. The aims of this study were to investigate the effects of PN on proliferation inhibition and induction of apoptosis, as well as the involvement of miRNAs in PN-mediated apoptosis in acute leukemia. The results showed that PN reduced cell viability and induced apoptosis in acute leukemia cells via both intrinsic and extrinsic pathways. A bioinformatics approach and Protein-Protein Interaction (PPI) network analysis revealed that ataxia-telangiectasia mutated kinase (ATM), one of the p53 activators that responds to DNA damage-induced apoptosis, is a crucial target of PN. Four prediction tools were used to predict ATM-regulated miRNAs; miR-181b-5p was the most likely candidate. The reduction in miR-181b-5 after PN treatment was found to trigger ATM, resulting in cellular apoptosis. Therefore, PN could be developed as a drug for acute leukemia; in addition, miR-181b-5p and ATM may be promising therapeutic targets.

Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia.

BACKGROUND: Punicalagin is the major phenolic compound found in pomegranate peels. It has several reported medical benefits, including antioxidant, anti-inflammatory, and anticancer properties. The present study investigated the anti-leukemic effects and the molecular mechanism of punicalagin on NB4 and MOLT-4 leukemic cell lines. METHODS: Leukemic cells were treated with punicalagin and cell viability was determined using MTS assay. Apoptosis and autophagy were analyzed by flow cytometry using Annexin V-FITC/PI and anti-LC3/FITC antibodies staining, respectively. Apoptotic and autophagic mRNA expression were determined using reverse transcription-quantitative PCR. STITCH bioinformatics tools were used to predict the interaction between punicalagin and its proposed target proteins. RESULTS: Results indicated that punicalagin decreased NB4 and MOLT-4 cell viability in a dose-dependent manner. Punicalagin, in combination with daunorubicin, exhibited synergistic cytotoxic effects. Punicalagin induced apoptosis through the upregulation of caspase-3/-8/-9, Bax and the downregulation of Bcl-2 expression. Punicalagin also promoted autophagy via the downregulation of mTOR and the upregulation of ULK1 expression. Cyclooxygenase-2 and toll-like receptor 4 were found to be involved in punicalagin-induced cell death in punicalagin-targeted protein interactions. CONCLUSIONS: These results suggest that punicalagin exerts cytotoxic activities by suppressing proliferation and promoting apoptosis and autophagy by activating the caspase cascade, altering Bax and Bcl-2, and regulating autophagy via mTOR/ULK1 signaling.

Bioactive peptide isolated from sesame seeds inhibits cell proliferation and induces apoptosis and autophagy in leukemic cells.

Leukemia is the most common type of hematological malignancies. Several natural products including bioactive peptides have been explored and studied for their anti-leukemic activities. In the present study, anti-leukemic peptide, IGTLILM (IM-7), was isolated and identified from the protein hydrolysate of sesame seeds by reverse phase-solid phase extraction, off-gel fractionation and nano LC-MS/MS. The cytotoxic effects of IM-7 were studied in MOLT-4 and NB4 acute leukemic cell lines using an MTT assay. The induction of apoptosis and autophagy was investigated by flow cytometry using Annexin V-FITC/PI staining and anti-LC3/FITC antibodies, respectively. The mRNA alterations of apoptotic and autophagic-related genes were determined by reverse transcription-quantitative PCR. The present study found that IM-7 inhibited the proliferation of MOLT-4 and NB4 cells in dose-dependent manner, but it showed a minimal effect on healthy mononuclear cells. IM-7 activated apoptosis and autophagy through the upregulation of CASP3, ULK1 and BECN1 and the downregulation of BCL2. In addition, IM-7 enhanced the cytotoxic effect of the anti-leukemic drug, daunorubicin. The findings suggested that IM-7 was potent to suppress the proliferation of MOLT-4 and NB4 leukemic cells and induce apoptosis and autophagy through the regulation of caspase 3-Bcl-2 and ULK1-Beclin1, respectively.