Anticancer Therapeutic Agents Research Articles

Retracted: Application of Artificial Intelligence in Discovery and Development of Anticancer and Antidiabetic Therapeutic Agents.

[This retracts the article DOI: 10.1155/2022/6201067.].

Antiproliferative activity and apoptosis-inducing mechanism of Curcuma longa (Turmimax®) on HeLa cell lines.

Curcumin, the primary polyphenol found in turmeric, is derived from the Curcuma longa plant. Since curcumin is nontoxic and has a wide range of medicinal qualities, including anti-oxidant, analgesic, anti-inflammatory, and antibacterial action, it has been widely employed in Ayurveda medicine for ages. Curcumin has recently been discovered to have anti-cancer properties through its impact on numerous biological pathways involved in carcinogenesis, metastasis, tumorigenesis, cell cycle regulation, mutagenesis, and oncogene expression. In this study, we determined the Antiproliferative activity and apoptosis-inducing mechanism of C. longa (Turmimax®) on human cancer cells. The cytotoxic effect was evaluated against HeLa cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Flow cytometric analysis was performed to detect apoptotic cell death. Turmimax® exhibits promising properties as a potential anti-cancer therapeutic agent in human cervical adenocarcinomas and possibly other cancer types, with an IC50 value of 87.89 µg/mL. In HeLa cells treated with Turmimax®, cell cycle arrest was seen in the G0/G1 and S phases. By inducing apoptosis and increasing the number of apoptotic cells in a dose-dependent manner, the experimental data suggest that Turmimax® has considerable promise in cancer prevention and treatment.

Evaluation of the Cytotoxicity of Cationic Polymers on Glioblastoma Cancer Stem Cells.

Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC's sensitivity to such compounds is thus described.

ANTI-CANCER PROPERTIES OF PHYTOCHEMICALS DERIVED FROM AZADIRACHTA INDICA: LITERATURE REVIEW

This study aims to assess the anti-cancer properties of phytochemicals derived from Azadirachta indica (neem), given the increasing prevalence of cancer and the need for safer and more effective therapies. Phytochemicals from Azadirachta indica have been reported to have potential as anti-cancer agents, but their mechanism of action is not fully understood. Therefore, this study was conducted to explore the anti-cancer potential of various phytochemicals extracted from Azadirachta indica. This study used literature review method supported by bibliometric analysis tools such as VOSviewer and Publish or Perish. The results showed that phytochemicals from Azadirachta indica have significant cytotoxic effects on cancer cells, as well as being able to induce apoptosis through intrinsic pathways. These results suggest that Azadirachta indica has the potential to be developed as an effective and safe anti-cancer therapeutic agent. Discussion of the results of this study highlights the importance of further development and clinical trials to validate these findings.

To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and Experiments.

Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein-protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment.

Despite therapeutic advancements, lung cancer remains the principal cause of cancer mortality in a global scenario. The increased incidence of tumor reoccurrence and progression and the highly metastatic nature of lung cancer are of great concern and hence require the investigation of novel therapies and/or medications. Naturally occurring compounds from plants serve as important resources for novel drugs for cancer therapy. Amongst these phytochemicals, Berberine, an alkaloid, has been extensively explored as a potential natural anticancer therapeutic agent. Several studies have shown the effectiveness of Berberine in inhibiting cancer growth and progression mediated via several different mechanisms, which include cell cycle arrest, inducing cell death by apoptosis and autophagy, inhibiting cell proliferation and invasion, as well as regulating the expression of microRNA, telomerase activity, and the tumor microenvironment, which usually varies for different cancer types. In this review, we aim to provide a better understanding of molecular insights of Berberine and its various derivative-induced antiproliferative and antimetastatic effects against lung cancer. In conclusion, the Berberine imparts its anticancer efficacy against lung cancers via modulation of several signaling pathways involved in cancer cell viability and proliferation, as well as migration, invasion, and metastasis.

Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review.

Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells’ antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells’ phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine–aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents.

Therapeutic Targeting of MYC in Head and Neck Squamous Cell Carcinoma

ABSTRACT MYC plays critical roles in tumorigenesis and is considered an attractive cancer therapeutic target. Small molecules that directly target MYC and are well tolerated in vivo represent invaluable anti-cancer therapeutic agents. Here, we aimed to investigate the therapeutic effect of MYC inhibitors in head and neck squamous cell carcinoma (HNSCC). The results showed that pharmacological and genetic inhibition of MYC inhibited HNSCC proliferation and migration. MYC inhibitor 975 (MYCi975), inhibited HNSCC growth in both cell line-derived xenograft and syngeneic murine models. MYC inhibition also induced tumor cell-intrinsic immune responses, and promoted CD8+ T cell infiltration. Mechanistically, MYC inhibition increased CD8+ T cell-recruiting chemokines by inducing the DNA damage related cGAS-STING pathway. High expression of MYC combined with a low level of infiltrated CD8+ T cell in HNSCC correlated with poor prognosis. These results suggested the potential of small-molecule MYC inhibitors as anti-cancer therapeutic agents in HNSCC.

Synthesis, docking studies, biological activity of carbon monoxide release molecules based on coumarin derivatives.

In the present work, we synthesized seven complexes. All complexes were identified by ESI-HRMS, 1H-NMR, 19F-NMR and 13C-NMR spectroscopies. The synthesized complexes were tested for their anticancer activities in vitro against three different human cell lines, including breast MDAMB231, cervical Hela, liver HepG2. IC50 values of complexes 1-7 were 34.98–667.35 µM. Complex 5 revealed higher sensitivity towards MDAMB231 cells with IC50 values 34.98 μM in comparison to 5-FU as positive control. Moreover, complex 5 caused a decrease of mitochondrial membrane potential and effectively induced ROS production against MDAMB231 cells. Western blot analysis showed that complex 5 could up-regulate the expression of Bax protein and down-regulate the expression of Bcl-2, activate Caspase-3, slightly down-regulate the expression of HO-1. The docking studies showed that complex 5 could be interacted with Bcl-2 protein through hydrophobic interactions, hydrogen bonds and salt bridges to enhance the binding affinity. All the analyzed coumarins obeyed the Lipinski’s rule of five for orally administered drugs. Based on the aforementioned results, it suggests that the complex induced apoptosis cell via mitochondria pathways. Collectively, complex 5 could be considered as a promising hit for new anti-breast cancer agents. Carbonyl cobalt CORMs, as potential anticancer therapeutic agents, provided a new idea for the development of metal anticancer drugs.

Multifunctional Plant Virus Nanoparticles for Targeting Breast Cancer Tumors.

Breast cancer treatment using plant-virus-based nanoparticles (PVNPs) has achieved considerable success in preclinical studies. PVNP-based breast cancer therapies include non-targeted and targeted nanoplatforms for delivery of anticancer therapeutic chemo and immune agents and cancer vaccines for activation of local and systemic antitumor immunity. Interestingly, PVNP platforms combined with other tumor immunotherapeutic options and other modalities of oncotherapy can improve tumor efficacy treatment. These applications can be achieved by encapsulation of a wide range of active ingredients and conjugating ligands for targeting immune and tumor cells. This review presents the current breast cancer treatments based on PVNP platforms.

Anti-proliferative Effects of Hydroxytyrosol Against Breast Cancer Cell Lines Through Induction of Apoptosis

Background: Due to high mortality of patients with metastatic breast cancer and limited strategies for management of this malignancy, development of novel therapeutic approaches and anti-cancer agents is essential. Objectives: In the present study, we investigated in vitro anti-proliferative effects of hydroxytyrosol, as a natural chemotherapeutic agent, against breast cancer cells MDA-MB-231 and MCF-7. Methods: The anti-proliferation activity of hydroxytyrosol on both MDA-MB-231 and MCF-7 breast cancer cells was evaluated by MTT assay. Apoptosis percentage was assessed by flow cytometry in the treated and untreated cancer cells. Moreover, the expression of three apoptotic genes (BAX, BCL2, and CASP3) was evaluated by real-time PCR in the treated cancer cells. Results: Our results indicated that hydroxytyrosol exerted an appropriate anti-proliferation activity on both MDA-MB-231 and MCF-7 cancer cells in a dose- and time-dependent manner. We observed a significant increase in apoptosis percentage in both treated cancer cells compared with untreated controls. In addition, hydroxytyrosol upregulated pro-apoptotic BAX and CASP3 genes while downregulated anti-apoptotic BCL2 gene. Conclusions: The findings of the present study suggested an appropriate anti-proliferation effect by hydroxytyrosol that may be due to apoptosis induction through modification of expression of apoptotic genes in breast cancer cells.

Transcriptional, chromatin, and metabolic landscapes of LDHA inhibitor-resistant pancreatic ductal adenocarcinoma.

Metabolic reprogramming, due in part to the overexpression of metabolic enzymes, is a key hallmark of cancer cells. Lactate dehydrogenase (LDHA), a metabolic enzyme that catalyzes the interconversion of lactate and pyruvate, is overexpressed in a wide variety of cancer types, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, the genetic or pharmacological inhibition of LDHA suppresses cancer growth, demonstrating a cancer-promoting role for this enzyme. Therefore, several pharmacological LDHA inhibitors are being developed and tested as potential anti-cancer therapeutic agents. Because cancer cells are known to rapidly adapt and become resistant to anti-cancer therapies, in this study, we modeled the adaptation of cancer cells to LDHA inhibition. Using PDAC as a model system, we studied the molecular aspects of cells resistant to the competitive LDHA inhibitor sodium oxamate. We performed unbiased RNA-sequencing (RNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC-seq), and metabolomics analyses of parental and oxamate-resistant PDAC cells treated with and without oxamate to identify the transcriptional, chromatin, and metabolic landscapes of these cells. We found that oxamate-resistant PDAC cells were significantly different from parental cells at the levels of mRNA expression, chromatin accessibility, and metabolites. Additionally, an integrative analysis combining the RNA-seq and ATAC-seq datasets identified a subset of differentially expressed mRNAs that directly correlated with changes in chromatin accessibility. Finally, functional analysis of differentially expressed metabolic genes in parental and oxamate-resistant PDAC cells treated with and without oxamate, together with an integrative analysis of RNA-seq and metabolomics data, revealed changes in metabolic enzymes that might explain the changes in metabolite levels observed in these cells. Collectively, these studies identify the transcriptional, chromatin, and metabolic landscapes of LDHA inhibitor resistance in PDAC cells. Future functional studies related to these changes remain necessary to reveal the direct roles played by these changes in the development of LDHA inhibitor resistance and uncover approaches for more effective use of LDHA inhibitors in cancer therapy.

Salvurmin A and Salvurmin B, Two Ursane Triterpenoids of Salvia urmiensis Induce Apoptosis and Cell Cycle Arrest in Human Lung Carcinoma Cells

Background: Ursane triterpenoids could be considered as novel multi-target therapeutic anti-cancer agents. Salvurmin A and Salvurmin B are novel cytotoxic ursane triterpenoids isolated from the aerial parts of Salvia urmiensis, an endemic plant species of Iran. Methods: In this study, we assessed cytotoxicity of these compounds against two human cancer cell lines and one human normal cell line and investigated its mechanism via apoptosis and cell cycle arrest. Results: Salvurmin A and B showed the most cytotoxic effect on A549 cells compared to other studied cancer cells. IC50 values for Salvurmin A and B against A549 cells were 35.6 ± 1.5 and 19.2 ± 0.8 µM, respectively. Based on annexin V staining, both of these compounds significantly induced apoptosis in A549 cells. Moreover, these two compounds significantly increased cell accumulation in G2/M and decreased the number of cells in G0/G1 phases in A549 cells in a dose-dependent manner. Conclusion: Based on the results Salvurmin B can be considered as potential candidate for further studies against human lung carcinoma.

Molecular structure, electronic properties, ESP map (polar aprotic and polar protic solvents), and topology investigations on 1-(tert‑Butoxycarbonyl)-3-piperidinecarboxylic acid- Anticancer therapeutic agent

The theoretical elucidation of 1-(tert‑Butoxycarbonyl)-3-piperidinecarboxylic acid (1TB3PC) was achieved in this work by using DFT/6–311++G(d,p) as the basis set level -B3LYP approach for the gas phase, polar aprotic, and protic solvents phases, respectively. Potential energy scan (PES) analysis and the optimized geometrical parameters for the gas, polar aprotic and polar protic solvent phases were attained and corresponding parameters were compared with the closely related molecule. The FMO's molecular orbitals (HOMO-LUMO) and the energy gap, FLU indices, and molecular electrostatic potential map (ESP) surface were carried out to predict the nucleophilic and electrophilic regions for the three phases (gas, polar aprotic, and polar protic solvents) were discussed. Further, the electron-hole distribution for the excited states and topological analyses (AIM, ELF, LOL and RDG) were also deliberated. To discern the biological activity of the title compound, drug likeness and ADMET predictions were carried out. Molecular docking approach was performed against ligand with various AKT /Protein Kinase B inhibitors targets and their corresponding parameters were conferred. Thus, the header composite designates as an alternative anticancer therapeutic agent.

Automated Capillary Isoelectric Focusing-Mass Spectrometry with Ultrahigh Resolution for Characterizing Microheterogeneity and Isoelectric Points of Intact Protein Complexes

Protein complexes are the functional machines in the cell and are heterogeneous due to protein sequence variations and post-translational modifications (PTMs). Here, we present an automated nondenaturing capillary isoelectric focusing-mass spectrometry (ncIEF-MS) methodology for uncovering the microheterogeneity of intact protein complexes. The method exhibited superior separation resolution for protein complexes than conventional native capillary zone electrophoresis (nCZE-MS). In our study, ncIEF-MS achieved liquid-phase separations and MS characterization of seven different forms of a streptavidin homotetramer with variations of N-terminal methionine removal, acetylation, and formylation and four forms of the carbonic anhydrase-zinc complex arising from variations of PTMs (succinimide, deamidation, etc.). In addition, ncIEF-MS resolved different states of an interchain cysteine-linked antibody-drug conjugate (ADC1) as a new class of anticancer therapeutic agents that bears a distribution of varied drug-to-antibody ratio (DAR) species. More importantly, ncIEF-MS enabled precise measurements of isoelectric points (pIs) of protein complexes, which reflect the surface electrostatic properties of protein complexes. We studied how protein sequence variations/PTMs modulate the pIs of protein complexes and how drug loading affects the pIs of antibodies. We discovered that keeping the N-terminal methionine residue of one subunit of the streptavidin homotetramer decreased its pI by 0.1, adding one acetyl group onto the streptavidin homotetramer reduced its pI by nearly 0.4, incorporating one formyl group onto the streptavidin homotetramer reduced its pI by around 0.3, and loading two more drug molecules on one ADC1 molecule increased its pI by 0.1. The data render the ncIEF-MS method a valuable tool for delineating protein complexes.

Cytotoxic and Antiproliferation Activity of n-Hexane Fraction of Avocado seed (Persea americana Mill.) on MCF7 cell

Avocado seeds, which often end up as food waste, have many health benefits, including anticancer activity. This study aimed to determine the potential cytotoxic activity of avocado seeds against breast cancer cells, MCF7. Avocado seeds were macerated with 96% ethanol and fractionated with n-hexane, chloroform, and ethyl acetate as solvents. Cytotoxic activity of the extract and fractions was tested using the MTT method, while antiproliferation activity and apoptosis of the n-hexane fraction were tested using the doubling time and double staining methods, respectively. The selectivity of the n-hexane fraction was also determined. The results showed that the extract and n-hexane fraction of avocado seeds had cytotoxic activity on MCF7 with IC50 values of 211.2±25 and 47.87±1.5 µg/mL, respectively. The cytotoxic activity of the n-hexane fraction was selective (Selectivity Index = 4.73). The fraction can extend the doubling time to 76.54-77.41 hours. The double staining test results showed red fluorescence in the cells, indicating the apoptosis of MCF7 cells. The n-hexane fraction of avocado seed extract has the potential to be developed as an anticancer therapeutic agent.

Fabrication of vitamin K3-carnosine peptide-loaded spun silk fibroin fibers/collagen bi-layered architecture for bronchopleural fistula tissue repair and regeneration applications.

Bronchial and pleural injuries with persistent air leak pose a threat in the repair and regeneration of pulmonary diseases. The need to arrive at a highly efficient therapy for closure of bronchopleural fistula (BPF) so as to effectively suppress inflammation, infection and repair the damaged pleural space caused by cancer as well as contractile restoration of bronchopleural scars remain a significant clinical challenge. Herein, we have designed and developed potent bioactive vitamin K3 carnosine peptide (VKC)-loaded spun SF fibroin fibers/collagen bi-layered 3D scaffold for bronchopleural fistula tissue engineering applications. The VKC drug showed excellent cell viability in human bronchial epithelial cells (HBECs), in addition to its pronounced higher cytotoxicity against the A549 lung cancer cell line with an IC50 of 5μg/mL. Furthermore, VKC displayed a strong affinity with the catalytic site of EGFR (PDB ID: 1M17) and VEGFR2 (PDB ID: 4AGD, 4ASD) receptors in molecular docking studies. Following which the spun SF-VKC (primary layer) and collagen film (top layer) constructed bi-layered CSVKC were structurally elucidated and its morphological, physicochemical and biological characterizations were well examined. The bi-layered scaffold showed superior biocompatibility and cell migration ability in HBECs than other scaffolds. Interestingly, the CSVKC revealed rapid HBECs motility towards scratched regions for fast healing in vitro bronchial tissue engineering. In vivo biocompatibility and angiogenesis studies of the prepared scaffolds were evaluated and the results obtained demonstrated excellent new tissue formation and neovascularization in the bi-layered architecture rather than others. Therefore, our results suggest that the potent antibacterial and anticancer therapeutic agent (VKC)-impregnated silk fibroin fibers/collagen bi-layered 3D biomaterial could be useful in treating cancerous BPF and pulmonary diseases in future.

In-vitro Assessment of Essential Oils as Anticancer Therapeutic Agents: A Systematic Literature Review

Cancer is a fatal disease that causes around 9 million deaths annually in developing and developed countries worldwide. Recently, natural products as alternatives for chemical agents have become a growing area of interest. Essential oils (EOs) are secondary metabolites of the plant, with a wide range of bioactivities, such as the anticancer effect. The present systematic review attempts to collect and document the recent studies from 01.01.2016 to 12.31.2020, indicating EOs as anticancer agents in in-vitro studies; data of 144 reports have been extracted. Anticancer effects of 187 distinct EOs on 112 cell lines were summarized; this is a valuable bank for researchers finding proper EO as an anticancer agent. Some EOs having comparable effects with conventional drugs have been suggested. These EOs are good candidates for further studies, such as in-vivo investigations.

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer.

Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.

TPEN selectively eliminates lymphoblastic B cells from bone marrow pediatric acute lymphoblastic leukemia patients.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.