melitten and Leukemia

Apitherapy is an emerging field in cancer research, particularly in developing communities. The potency of Melittin (MEL), a major constituent in bee venom is accounted for the cytotoxic capacity against cancer cells. It is postulated that the genotype of bees and the time of venom collection influences its specific activity against certain types of cancer.. Hereby, Jordanian crude bee venom (JCBV) was collected during different seasons of the year, specifically spring, summer and autumn and investigated for in vitro antitumour effects. Venom collected during springtime comprised the highest quantity of MEL in comparison to venom collected some other time. Springtime-collected JCBV extract and MEL were tested on an immortal myelogenous leukaemia cell line, namely K562 leukemic cells. Treated cells were examined for cell modality via flow cytometry analysis and cell death mediating gene expressions.. Integration of bee venom in chemotherapy needs more investigation and should be carefully translated into clinical use. During such translation, the correlation of bee genotype, collection time and concentration of MEL in CBV should be profiled.

Topics: Animals; Bee Venoms; Bees; Humans; K562 Cells; Leukemia; Melitten; Peptides

The creation of brand-new, potent, and less harmful medications to treat leukemia is urgently needed. Antimicrobial peptides (AMPs) have drawn a lot of interest as potential substitutes for chemotherapy.. In the present investigation, the anticancer activity of CM11, a short cationic AMP, was assessed on Jurkat and Raji leukemia cell lines and peripheral blood mononuclear cells (PBMCs).. Different CM11 doses were applied to the Jurkat and Raji cell lines and PBMCs throughout a 24-hour period. The impact of the CM11 on cell viability and toxicity was assessed using an MTT assay. Flow cytometry and Real-Time PCR were used to analyze the effect of this peptide on apoptotic/necrosis pathways and assess the ratio expression of the. Despite the fact that peptide toxicity was successful in a variety of cell lines, cancer cells were more sensitive to the medication. The survival of Jurkat and Raji cell lines treated with 32 μg/ml peptide was 47% and 51%, respectively, while the survival of normal PBMC cells was about 65%. According to flow cytometry, Jurkat and Raji cells exposed to peptide had much greater levels of apoptosis than PBMCs. Peptide-treated cells were associated with increased expression of. These results revealed that the CM11 caused more cytotoxicity to leukemia Raji and Jurkat leukemia cells compared to the normal cells by apoptosis pathway. Our findings demonstrated the potential of CM11 peptide to develop as a new antileukemic agent.

Topics: Apoptosis; Cecropins; Cell Line, Tumor; Humans; Jurkat Cells; Leukemia; Leukocytes, Mononuclear; Melitten; Peptides; Tumor Suppressor Protein p53

Activation of cytosolic phospholipase A2 (cPLA2) by TNF has been shown to be an important component of the signaling pathway leading to cell death. The role of cPLA2 in the cytotoxic action of TNF was investigated in a panel of human leukemic cell lines. TNF could activate cPLA2 only in U937 and HL60 TNF-sensitive leukemic cells, but not in KG1a, CEM, and CEM/VLB100 cells that are relatively resistant to TNF. Pretreatment with 4-bromophenacyl bromide, a cPLA2 inhibitor, rendered U937 and HL60 cell lines resistant to the cytotoxic effect of TNF. Immunoblot and reverse-transcriptase PCR demonstrated that cPLA2 expression was detectable at both transcriptional and translational levels in all leukemic cell lines studied, although CEM and CEM/VLB100 cells expressed cPLA2 mRNA and protein at lower levels. The protein synthesis inhibitor, cycloheximide, increased TNF-induced cPLA2 activity and cytotoxicity in both CEM and CEM/VLB100 cell lines. Low levels of cPLA2 activity in the KG1a cell line could be activated by the cPLA2 activator mellitin, or the calcium ionophore A23187. The data suggest that cPLA2 activity is involved in TNF-induced cytotoxicity in leukemic cells. Resistance to TNF-induced cytotoxicity may involve either protein inhibitors that act upstream of cPLA2 in the TNF-signaling pathway or constitutive defects of cPLA2 itself, possibly involving calcium utilization.

Topics: Acetophenones; Antigens, CD; Apoptosis; Arachidonic Acid; Calcimycin; Cytosol; Drug Resistance, Neoplasm; Enzyme Activation; Enzyme Inhibitors; HL-60 Cells; Humans; Leukemia; Melitten; Phospholipases A; Phospholipases A2; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction; Tumor Necrosis Factor-alpha

Calmodulin, a ubiquitous calcium-binding protein, has recently been shown to play an important role in cellular proliferation. The calmodulin inhibitors melittin, trifluoperazine, and chlorpromazine inhibited the growth and clonogenicity of human and murine leukemic cells, and their potency reflected their activity as inhibitors of calmodulin. Melittin, which is a far more potent inhibitor of calmodulin activity, was also a more potent inhibitor of cell growth and clonogenicity. The less active phenothiazine metabolite, chlorpromazine sulfoxide, had much less potent cytotoxic activity.

Topics: Animals; Bee Venoms; Calmodulin; Cell Division; Humans; Leukemia; Melitten; Mice; Phenothiazines