Encapsulation of daunorubicin into Saccharomyces cerevisiae-derived lysosome as drug delivery vehicles for acute myeloid leukemia (AML) treatment

Choi, Wooil; Heo, Mi Young; Kim, Sang Yong; Wee, Ji‐Hyang; Kim, Yang‐Hoon; Min, Jiho

doi:10.1016/j.jbiotec.2019.12.008

Cited by 23 publications

(17 citation statements)

References 16 publications

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“…By using the S. cerevisiae-derived vacuole used in the present study, it was possible to target cancer and effectively deliver anticancer drugs, and research is being actively conducted as new therapeutic material such as increasing anticancer and antibacterial effects through gene recombination [7,15]. However, studies on the immunological effects of S. cerevisiae-derived vacuoles are insufficient.…”

Section: Discussionmentioning

confidence: 99%

“…We investigated whether vacuoles penetrate into RAW 264.7 cells by treatment with the vacuole extract of recombinant yeast strain YPT7 (Figure 2C). YPT7 protein is located in the membrane of the vacuole and a transformed yeast recombinant plasmid with GFP attached, pYES2.0::YPT7::GFP was used [7]. At this time, the location of the vacuole can be confirmed through the signal of GFP.…”

Section: Effect Of Vacuole On the No Production And Protein Expression Of Inos And Cox-2mentioning

confidence: 99%

“…Various studies have been conducted for use as a therapeutic agent, such as an ecofriendly antibacterial agent using vacuole, or an anticancer agent using lysosome [6,7]. To apply this treatment to animals or humans, we tried to determine the effect of vacuoles on the immune system.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced immune response by vacuoles isolated fromSaccharomyces cerevisiaein RAW 264.7 macrophages

et al. 2021

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Vacuoles are membrane vesicles in eukaryotic cells, the digestive system of cells that break down substances absorbed outside the cell and digest the useless components of the cell itself. Researches on anticancer and intractable diseases using vacuoles are being actively conducted. The practical application of the present study to animals requires the determination of the biocompatibility of vacuole. In the present study, we evaluated the effects of vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 cells. This showed a significant increase in the production of nitric oxide (NO) produced by macrophage activity. Using Reactive Oxygen Species (ROS) assay, we identified that ROS is increased in a manner dependent on vacuole concentration. Western blot analysis showed that vacuole concentration-dependently increased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). Therefore, iNOS expression was stimulated to induce NO production. In addition, pro-inflammatory cytokines levels promoted, such as interleukin (IL) 6 (IL-6) and tumor necrosis factor (TNF) α (TNF-α). In summary, vacuoles activate the immune response of macrophages by promoting the production of immune-mediated transporters NO, ROS, and pro-inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Vacuole On the No Production And Protein Expression Of Inos And Cox-2mentioning

confidence: 99%

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Enhanced immune response by vacuoles isolated fromSaccharomyces cerevisiaein RAW 264.7 macrophages

et al. 2021

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“…Lysosomes, due to their robustness within the biological environment and low immunogenic reaction can serve as a suitable carrier. Yeast-derived lysosomes, engineered to carry the anthracycline drug, daunorubicin, have exhibited efficacy against the AML cell line, HL60 [103].…”

Section: Other Novel Approachesmentioning

confidence: 99%

Lysosomes in acute myeloid leukemia: potential therapeutic targets?

et al. 2021

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Lysosomes, since their discovery, have been primarily known for degrading cellular macromolecules. However, in recent studies, they have begun to emerge as crucial regulators of cell homeostasis. They are at the crossroads of catabolic and anabolic pathways and are intricately involved in cellular trafficking, nutrient signaling, energy metabolism, and immune regulation. Their involvement in such essential cellular functions has renewed clinical interest in targeting the lysosome as a novel way to treat disease, particularly cancer. Acute myeloid leukemia (AML) is an aggressive blood cancer with a low survival probability, particularly in older patients. The genomic landscape of AML has been extensively characterized but few targeted therapies (with the exception of differentiation therapy) can achieve a long-term cure. Therefore, there is an unmet need for less intensive and more tolerable therapeutic interventions. In this review, we will give an overview on the myriad of functions performed by lysosomes and their importance in malignant disease. Furthermore, we will discuss their relevance in hematopoietic cells and different ways to potentially target them in AML.

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“…Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies, with the highest incidence in adults ( Short et al, 2018 ). Despite advancements in the biological understanding of AML, the standard treatment has not significantly improved over 40 years ( Choi et al, 2020 ). The prognosis remains dismal, and most patients encounter disease recurrence or die of the disease several months after their initial remission.…”

Section: Introductionmentioning

confidence: 99%

Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia

Ding

Liang

Cheng

et al. 2021

Front. Cell Dev. Biol.

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Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with AML using the data downloaded from The Cancer Genome Atlas (TCGA) database.Methods: The RNA-seq and clinical data were obtained from the TCGA AML cohort. First, Pearson correlation analysis was performed to identify the m6A-related lncRNAs. Next, univariate Cox regression analysis was used to determine the candidate lncRNAs with prognostic value. Then, feature selection was carried out by Least absolute shrinkage and selection operator (LASSO) analysis, and seven eligible m6A-related lncRNAs were included to construct the prognostic risk signature. Kaplan–Meier and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive capacity of the risk signature both in the training and testing datasets. A nomogram was used to predict 1-year, 2-year, and 3-year overall survival (OS) of AML patients. Next, the expression levels of lncRNAs in the signature were validated in AML samples by qRT-PCR. Functional enrichment analyses were carried out to identify probable biological processes and cellular pathways. The ceRNA network was developed to explore the downstream targets and mechanisms of m6A-related lncRNAs in AML.Results: Seven m6A-related lncRNAs were identified as a prognostic signature. The low-risk group hold significantly prolonged OS. The nomogram showed excellent accuracy of the signature for predicting 1-year, 2-year and 3-year OS (AUC = 0.769, 0.820, and 0.800, respectively). Moreover, the risk scores were significantly correlated with enrichment in cancer hallmark- and malignancy-related pathways and immunotherapy response in AML patients.Conclusion: We developed and validated a novel risk signature with m6A-related lncRNAs which could predict prognosis accurately and reflect the immunotherapy response in AML patients.

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Encapsulation of daunorubicin into Saccharomyces cerevisiae-derived lysosome as drug delivery vehicles for acute myeloid leukemia (AML) treatment

Cited by 23 publications

References 16 publications

Enhanced immune response by vacuoles isolated fromSaccharomyces cerevisiaein RAW 264.7 macrophages

Enhanced immune response by vacuoles isolated fromSaccharomyces cerevisiaein RAW 264.7 macrophages

Lysosomes in acute myeloid leukemia: potential therapeutic targets?

Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia

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