Increased susceptibility to doxorubicin-induced cell death in acute lymphocytic leukemia cells by inhibiting serine/threonine WEE1 kinase expression using the chitosan-carboxymethyl dextran-polyethylene glycol-TAT nanoparticles

Feizi, Abbas Ali Hosseinpour; Vakili-Samiani, Sajjad; Masjedi, Ali; Izadi, Sepideh; Adibfar, Sara; Nikkhoo, Afshin; Hojjat‐Farsangi, Mohammad; Atyabi, Fatemeh; Khanghah, Omid Joodi; Movassaghpour, Ali Akbar; Solali, Saeed; Yousefi, Mehdi; Karpisheh, Vahid

doi:10.1016/j.jddst.2022.103868

Cited by 5 publications

(13 citation statements)

References 47 publications

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“…In the current study, CCMD-PEG-TAT NPs were used to deliver Ara-c and siRNAs against HO-1 and HIF-1 into the leukemic cells. As demonstrated by our previous study, these NPs are highly effective in transfecting hematological malignant cells [22]. The presence of TAT increases the e ciency of this transfection [22].…”

Section: Transfection Of Cells With Nps Loaded With Sirna and Ara-cmentioning

confidence: 55%

“…As demonstrated by our previous study, these NPs are highly effective in transfecting hematological malignant cells [22]. The presence of TAT increases the e ciency of this transfection [22]. The cells were cultivated and then treated with one of the following pharmacological compounds for 24 (for qRT-PCR, MTT test), 48 h (for MTT test), and 72 h (for protein analysis); Untreated, NP-HIF-1α siRNA, NP-HO-1 siRNA, NP-HO-1+HIF-1α siRNA, Ara-c, NP-Ara-c, NP-HO-1 siRNA-Ara-c, NP-HIF-1α siRNA-Ara-c, NP-HIF-1α+HO-1 siRNA+Ara-c. For each treatment group, 50 nM of each siRNA was used.…”

Section: Transfection Of Cells With Nps Loaded With Sirna and Ara-cmentioning

confidence: 59%

“…Although siRNAs can inhibit gene expression, they are poorly unstable due to degradation by phosphatases and RNases [21]. To e ciently transfect cells with siRNA and increase the stability of siRNAs, we used our recently developed nanoparticles (NPs) [22]. NPs increment the solvency of medications and diminish the necessary successful dose [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…TAT usage increases the e ciency of transfection. All the necessary tests on NPs to ensure the e cient delivery of the therapeutics to the leukemic cells were performed in our previous study [22].…”

Section: Introductionmentioning

confidence: 99%

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The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and Hypoxia-inducible factor 1-alpha

Sadeghi,

Moslehi,

Kheiry

et al. 2024

Preprint

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Background Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. A main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. Method In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. Results The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. Conclusions As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.

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Section: Transfection Of Cells With Nps Loaded With Sirna and Ara-cmentioning

confidence: 55%

Section: Transfection Of Cells With Nps Loaded With Sirna and Ara-cmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and Hypoxia-inducible factor 1-alpha

Sadeghi,

Moslehi,

Kheiry

et al. 2024

Preprint

Self Cite

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“…In the instance of acute lymphocytic leukemia, leukemia cells displayed enhanced vulnerability to doxorubicin-induced cell death. The drug's ability to suppress serine/threonine WEE1 kinase expression utilizing chitosan-carboxymethyl dextran-polyethylene glycol-TAT nanoparticles provided evidence that it may be used as a potent anti-cancer therapeutic [61]. Isolation of cells from the tumor microenvironment is crucial in stem cell-based cancer therapy.…”

Section: Nanotherapy In Drug Deliverymentioning

confidence: 99%

Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics

et al. 2023

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Nano-oncology is a branch of biomedical research and engineering that focuses on using nanotechnology in cancer diagnosis and treatment. Nanomaterials are extensively employed in the field of oncology because of their minute size and ultra-specificity. A wide range of nanocarriers, such as dendrimers, micelles, PEGylated liposomes, and polymeric nanoparticles are used to facilitate the efficient transport of anti-cancer drugs at the target tumor site. Real-time labeling and monitoring of cancer cells using quantum dots is essential for determining the level of therapy needed for treatment. The drug is targeted to the tumor site either by passive or active means. Passive targeting makes use of the tumor microenvironment and enhanced permeability and retention effect, while active targeting involves the use of ligand-coated nanoparticles. Nanotechnology is being used to diagnose the early stage of cancer by detecting cancer-specific biomarkers using tumor imaging. The implication of nanotechnology in cancer therapy employs photoinduced nanosensitizers, reverse multidrug resistance, and enabling efficient delivery of CRISPR/Cas9 and RNA molecules for therapeutic applications. However, despite recent advancements in nano-oncology, there is a need to delve deeper into the domain of designing and applying nanoparticles for improved cancer diagnostics.

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The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha

Sadeghi,

Moslehi,

Kheiry

et al. 2024

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

Background Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. Method In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. Results The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. Conclusions As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.

show abstract

Increased susceptibility to doxorubicin-induced cell death in acute lymphocytic leukemia cells by inhibiting serine/threonine WEE1 kinase expression using the chitosan-carboxymethyl dextran-polyethylene glycol-TAT nanoparticles

Cited by 5 publications

References 47 publications

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and Hypoxia-inducible factor 1-alpha

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and Hypoxia-inducible factor 1-alpha

Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha

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