Abstract
Background: 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.
Objective: 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).
Methods: 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 P53 and Bcl-2 genes, respectively.
Results: 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 P53 the gene and decreased expression of the Bcl-2 gene.
Conclusion: 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.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.3390/molecules23112845] [PMID: 30388846]
[http://dx.doi.org/10.1080/10428194.2017.1354372] [PMID: 28745565]
[http://dx.doi.org/10.1007/s00018-005-4560-2] [PMID: 15868403]
[http://dx.doi.org/10.1016/j.blre.2010.04.001] [PMID: 20471733]
[http://dx.doi.org/10.1124/mol.115.100206] [PMID: 26519223]
[http://dx.doi.org/10.1016/S0378-4274(01)00329-0] [PMID: 11369469]
[http://dx.doi.org/10.18632/oncotarget.25718] [PMID: 30100992]
[http://dx.doi.org/10.3389/fmicb.2013.00294] [PMID: 24101917]
[http://dx.doi.org/10.1097/MRM.0000000000000032]
[http://dx.doi.org/10.18632/oncotarget.16743] [PMID: 28422728]
[http://dx.doi.org/10.2174/1574892814666190119165157] [PMID: 30663573]
[http://dx.doi.org/10.2174/1568026619666190125161517] [PMID: 30686254]
[http://dx.doi.org/10.3390/biom8010004] [PMID: 29351202]
[http://dx.doi.org/10.3389/fcimb.2016.00194] [PMID: 28083516]
[http://dx.doi.org/10.1016/j.chemphyslip.2015.02.003] [PMID: 25707312]
[http://dx.doi.org/10.1007/s11696-023-02735-1]
[http://dx.doi.org/10.1016/j.ejphar.2009.08.043] [PMID: 19835863]
[http://dx.doi.org/10.1089/mdr.2017.0392] [PMID: 29957118]
[http://dx.doi.org/10.1007/s12602-012-9098-7] [PMID: 26781855]
[http://dx.doi.org/10.1016/0014-5793(92)80377-S] [PMID: 1733777]
[http://dx.doi.org/10.1021/bi953058c] [PMID: 8703963]
[http://dx.doi.org/10.1007/s11274-013-1575-y] [PMID: 24323118]
[http://dx.doi.org/10.3389/fchem.2017.00005] [PMID: 28271058]
[http://dx.doi.org/10.1099/jmm.0.000524] [PMID: 28699872]
[http://dx.doi.org/10.1002/0471142735.im0701s85]
[http://dx.doi.org/10.1007/s10989-017-9658-5]
[http://dx.doi.org/10.1186/s41241-017-0014-z]
[http://dx.doi.org/10.1016/j.bbamem.2007.11.008]
[http://dx.doi.org/10.3390/ph14070687] [PMID: 34358113]
[http://dx.doi.org/10.2147/DDDT.S207224] [PMID: 31308628]
[http://dx.doi.org/10.1016/j.peptides.2010.05.010] [PMID: 20493915]
[http://dx.doi.org/10.1128/AAC.00925-06] [PMID: 17158938]
[http://dx.doi.org/10.1016/j.biochi.2018.02.001] [PMID: 29427740]
[http://dx.doi.org/10.1016/j.ejphar.2017.03.054] [PMID: 28347740]
[http://dx.doi.org/10.3109/10428194.2013.770847] [PMID: 23350892]
[http://dx.doi.org/10.1242/dmm.007310] [PMID: 21729875]
[http://dx.doi.org/10.1007/s10863-020-09846-4] [PMID: 32715369]
[http://dx.doi.org/10.1080/10428194.2017.1344839] [PMID: 28679301]
[http://dx.doi.org/10.1038/nm0697-614] [PMID: 9176486]
[http://dx.doi.org/10.2174/1389557514666141107120954] [PMID: 25382016]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2359] [PMID: 23100468]
[http://dx.doi.org/10.1016/j.toxicon.2019.06.016] [PMID: 31229626]
[http://dx.doi.org/10.1016/j.lfs.2013.03.016] [PMID: 23583573]
[http://dx.doi.org/10.1139/bcb-2016-0094] [PMID: 28169560]
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0274] [PMID: 19435812]
[http://dx.doi.org/10.1007/s11051-020-04838-2]