Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia
Abstract Acute leukemia has rapid onset and severe complications. Anticancer peptides from natural sources have demonstrated efficacy in eliminating various cancers through apoptosis signaling pathways. Additionally, extracellular vesicles containing microRNAs play pivotal roles in promoting tumorig...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-78082-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846171960110743552 |
|---|---|
| author | Kantorn Charoensedtasin Chosita Norkaew Mashima Naksawat Wasinee Kheansaard Sittiruk Roytrakul Dalina Tanyong |
| author_facet | Kantorn Charoensedtasin Chosita Norkaew Mashima Naksawat Wasinee Kheansaard Sittiruk Roytrakul Dalina Tanyong |
| author_sort | Kantorn Charoensedtasin |
| collection | DOAJ |
| description | Abstract Acute leukemia has rapid onset and severe complications. Anticancer peptides from natural sources have demonstrated efficacy in eliminating various cancers through apoptosis signaling pathways. Additionally, extracellular vesicles containing microRNAs play pivotal roles in promoting tumorigenesis. Therefore, this study aimed to investigate the impact of PG2, a pomegranate peptide that regulates extracellular vesicles, on the induction of acute leukemia cell apoptosis. NB4 and MOLT-4 leukemia cell lines were treated with PG2 alone or in combination with daunorubicin to assess cell viability using the MTT assay. Extracellular vesicles were extracted from PG2-treated NB4 and MOLT-4 cells. Bioinformatic tools were utilized to predict target proteins and microRNAs, following which mRNA and protein expression were determined by using RT‒qPCR and western blotting, respectively. PG2 significantly reduced the viability of NB4 and MOLT-4 cells. Furthermore, the combination of PG2 with daunorubicin had a synergistic effect on NB4 and MOLT-4 cells. Subsequent treatment with PG2 or PG2-treated extracellular vesicles decreased CDK2 expression while increasing microRNA-339-5p and caspase-3 expression in NB4 and MOLT-4 cells. Our findings revealed that the anticancer activity of PG2 through the CDK2/miR-339-5p/caspase-3 pathway is mediated by extracellular vesicles, ultimately inducing apoptosis. PG2 holds promise as a potential antileukemic drug. |
| format | Article |
| id | doaj-art-716d30b27cd14806a6ab0ef5951a5f0d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-716d30b27cd14806a6ab0ef5951a5f0d2024-11-10T12:26:02ZengNature PortfolioScientific Reports2045-23222024-11-0114111210.1038/s41598-024-78082-2Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemiaKantorn Charoensedtasin0Chosita Norkaew1Mashima Naksawat2Wasinee Kheansaard3Sittiruk Roytrakul4Dalina Tanyong5Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol UniversityDepartment of Clinical Microscopy, Faculty of Medical Technology, Mahidol UniversityDepartment of Clinical Microscopy, Faculty of Medical Technology, Mahidol UniversityDepartment of Clinical Microscopy, Faculty of Medical Technology, Mahidol UniversityFunctional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development AgencyDepartment of Clinical Microscopy, Faculty of Medical Technology, Mahidol UniversityAbstract Acute leukemia has rapid onset and severe complications. Anticancer peptides from natural sources have demonstrated efficacy in eliminating various cancers through apoptosis signaling pathways. Additionally, extracellular vesicles containing microRNAs play pivotal roles in promoting tumorigenesis. Therefore, this study aimed to investigate the impact of PG2, a pomegranate peptide that regulates extracellular vesicles, on the induction of acute leukemia cell apoptosis. NB4 and MOLT-4 leukemia cell lines were treated with PG2 alone or in combination with daunorubicin to assess cell viability using the MTT assay. Extracellular vesicles were extracted from PG2-treated NB4 and MOLT-4 cells. Bioinformatic tools were utilized to predict target proteins and microRNAs, following which mRNA and protein expression were determined by using RT‒qPCR and western blotting, respectively. PG2 significantly reduced the viability of NB4 and MOLT-4 cells. Furthermore, the combination of PG2 with daunorubicin had a synergistic effect on NB4 and MOLT-4 cells. Subsequent treatment with PG2 or PG2-treated extracellular vesicles decreased CDK2 expression while increasing microRNA-339-5p and caspase-3 expression in NB4 and MOLT-4 cells. Our findings revealed that the anticancer activity of PG2 through the CDK2/miR-339-5p/caspase-3 pathway is mediated by extracellular vesicles, ultimately inducing apoptosis. PG2 holds promise as a potential antileukemic drug.https://doi.org/10.1038/s41598-024-78082-2PomegranateMicroRNAExtracellular vesiclesApoptosisLeukemia |
| spellingShingle | Kantorn Charoensedtasin Chosita Norkaew Mashima Naksawat Wasinee Kheansaard Sittiruk Roytrakul Dalina Tanyong Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia Scientific Reports Pomegranate MicroRNA Extracellular vesicles Apoptosis Leukemia |
| title | Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia |
| title_full | Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia |
| title_fullStr | Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia |
| title_full_unstemmed | Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia |
| title_short | Anticancer effects of pomegranate-derived peptide PG2 on CDK2 and miRNA-339-5p-mediated apoptosis via extracellular vesicles in acute leukemia |
| title_sort | anticancer effects of pomegranate derived peptide pg2 on cdk2 and mirna 339 5p mediated apoptosis via extracellular vesicles in acute leukemia |
| topic | Pomegranate MicroRNA Extracellular vesicles Apoptosis Leukemia |
| url | https://doi.org/10.1038/s41598-024-78082-2 |
| work_keys_str_mv | AT kantorncharoensedtasin anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia AT chositanorkaew anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia AT mashimanaksawat anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia AT wasineekheansaard anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia AT sittirukroytrakul anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia AT dalinatanyong anticancereffectsofpomegranatederivedpeptidepg2oncdk2andmirna3395pmediatedapoptosisviaextracellularvesiclesinacuteleukemia |