Search Results (210)

Despite the successes achieved in recent years in the treatment of childhood acute lymphoblastic leukemia (ALL), high-risk ALL in particular still represents a considerable challenge, with poorer outcomes. The PI3K/AKT/mTOR signaling pathway is frequently constitutively activated in ALL and consequently leads to unrestricted cell proliferation, without showing frequent mutations in the most important representatives of the signaling pathway. Recent studies have shown that fine balanced protein expression is a common way to adjust oncogenic B cell directed receptor signaling and to mediate malignant cell proliferation and survival in leukemic cells. Too low expression of inhibitory phosphatases can lead to constitutive signaling of kinases, which are important for cell proliferation and survival. In contrast, marked high expression levels of key phosphatases enable cells with distinct pronounced oncogenic B cell directed receptor signaling to escape negative selection by attenuating signal strength and thus raising the threshold for deletion checkpoint activation. One of the most important B cell receptor-dependent signaling cascades is the PI3K/AKT signaling pathway, with its important antagonist SHIP1. However, recent data show that the inositol-5-phosphatase SHIP1 is differentially expressed across the heterogeneity of the ALL subtypes, making the overall therapeutic strategy targeting SHIP1 more complex. The aim of this article is therefore to provide an overview of the current knowledge about SHIP1, its expression in the various subtypes of ALL, its regulation, and the molecules that influence its gene and protein expression, to better understand its role in the pathogenesis of leukemia and other human cancers. Full article

In this study, 3-chlorothiophene-2-carboxylic acid (HL) was used as a main ligand to successfully synthesize four novel complexes: [Cu(L)₂(Py)₂(OH₂)₂] (1), [Co(L)₂(Py)₂(OH₂)₂] (2) (Py = pyridine), [{Ni(L)₂(OH₂)₄}₂{Ni(L)(OH₂)₅}]L•5H₂O (3), and [{Co(L)₂(OH₂)₄}₂{Co(L)(OH₂)₅}]L•5H₂O (4). All four compounds were identified by elemental analysis and ESI mass spectrometry, and subsequently characterized by IR spectroscopy, UV-visible diffuse reflectance spectroscopy, electron paramagnetic resonance spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography, and cyclic voltammetry. X-ray analyses revealed that complexes 1 and 2 exhibit a centrosymmetric pseudo-octahedral coordination geometry; the copper (II) and cobalt (II) metal ions, respectively, are located at the crystallographic center of inversion. The coordination sphere of the copper (II) complex is axially elongated in accordance with the Jahn–Teller effect. Intriguingly, for charge neutrality, compounds 3 and 4 crystallized as three independent mononuclear octahedrally coordinated metal centers, which are two $\left[\mathrm{M}{\mathrm{L}}_2{\left({\mathrm{O}\mathrm{H}}_2\right)}_4\right]$ complex molecules and one ${\left[\mathrm{M}\mathrm{L}{\left({\mathrm{O}\mathrm{H}}_2\right)}_5\right]}^{+}$ complex cation (M = ${\mathrm{N}\mathrm{i}}^{\mathrm{I}\mathrm{I}}$ and ${\mathrm{C}\mathrm{o}}^{\mathrm{I}\mathrm{I}}$, respectively), with the ligand anion ${\mathrm{L}}^{-}$ serving as the counter ion. The anticancer activities of these complexes were systematically assessed on human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. Among them, complex 4 shows significant inhibitory effects on leukemia K562 cells and colon cancer SW480 cells. Full article

Background: MYB is a key transcription factor that plays an essential role in regulating hematopoiesis, particularly influencing cell proliferation, differentiation, and apoptosis. It has been extensively implicated in the pathogenesis and progression of leukemia, as well as in determining patient prognosis and responsiveness to chemotherapy. Despite these well-documented roles, the precise molecular mechanisms by which MYB contributes to chemotherapy resistance in leukemia remain largely undefined. Methods: In this study, we investigated the potential role of MYB in regulating ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, which has recently emerged as a novel therapeutic target in cancer. We overexpressed and knockdown MYB in human leukemia K562 cells and evaluated changes in ferroptosis-related markers, as well as cell proliferation and migration capacities, in the context of treatment with the chemotherapeutic agent sorafenib. Results: Our findings demonstrated that MYB overexpression significantly enhanced the resistance of human leukemia cells to sorafenib, while MYB knockdown increased their drug sensitivity. Mechanistically, MYB was found to upregulate ferritin heavy chain 1 (FTH1), thereby suppressing sorafenib-induced ferroptosis and cell death. Further, FTH1 knockdown significantly reduced the proliferation and migration ability of K562 cells and enhanced sorafenib-induced ferroptosis. Rescue experiments confirmed that FTH1 is required for MYB induced sorafenib resistance and ferroptosis inhibition in human leukemia cells. Conclusions: Collectively, this study identifies the MYB-FTH1 axis as a novel regulatory pathway modulating ferroptosis and chemoresistance in leukemia cells, providing potential therapeutic targets for improving treatment precision and preventing disease relapse. Full article

Carboxamide derivatives are a promising class of compounds in anticancer drug discovery, owing to their ability to interact with multiple oncogenic targets and their favorable pharmacological profiles. In this study, we report the design, synthesis, and biological evaluation of a series of N-substituted 1H-indole-2-carboxamides as potential anticancer agents. The synthesized compounds were assessed for antiproliferative activity using the MTT assay against MCF-7 (breast cancer), K-562 (leukemia), and HCT-116 (colon cancer) cell lines, with normal human dermal fibroblasts included as a non-cancerous control. Several compounds demonstrated notable cytotoxicity and selectivity. Compounds 12, 14, and 4 exhibited potent activity against K-562 cells, with IC₅₀ values of 0.33 µM, 0.61 µM, and 0.61 µM, respectively. Compound 10 showed the most significant activity against HCT-116 cells (IC₅₀ = 1.01 µM) with a high selectivity index (SI = 99.4). Moderate cytotoxicity was observed against MCF-7 cells. To elucidate the mechanism of action, molecular docking and induced-fit docking studies were conducted against key cancer-related targets, including topoisomerase–DNA (PDB ID: 5ZRF), PI3Kα (4L23), and EGFR (3W32), revealing favorable binding interactions. Additionally, principal component analysis of molecular descriptors indicated that the compounds possess promising drug-like and lead-like properties, particularly compound 10. Overall, this study highlights N-substituted indole-2-carboxamides as promising scaffolds for further optimization. The integration of synthetic chemistry, biological assays, and computational modeling provides a robust foundation for the continued development of these compounds as potential anticancer agents. Full article

Reciprocal signaling between acute myeloid leukemia (AML) cells and the surrounding bone-marrow microenvironment (BMME) promotes AML progression through several mechanisms. One of the most important mechanisms is the induction of Galectin-3 (Gal-3) expression by AML cells and bone marrow mesenchymal stromal cells (BM-MSCs). Emerging evidence indicates that Gal-3 upregulation in the BMME promotes AML cell adhesion and survival, leading to the development of chemotherapy resistance, relapse, and poor prognosis. Identifying the biological function and critical signaling pathways of Gal-3 may contribute to overcoming acquired drug resistance and preventing post-treatment relapse. Gal-3 is involved in several molecular signaling pathways, including PI3K/AKT/mTOR, Ras/Raf/MEK/ERK, JAK/STAT, JNK, Wnt/β-catenin, PLC/PKC and NF-κB, which are interconnected to promote AML cell survival and resistance to chemotherapy. This review focuses on the biological effects, molecular mechanisms of action and regulation of Gal-3 in the pathogenesis and progression of AML. The therapeutic potential of potent synthetic small-molecule Gal-3 inhibitors in high-risk patients with AML is also discussed based on preclinical and clinical evidence from several human diseases. Currently, the effect of these Gal-3 inhibitors in AML has not been investigated either in vitro or in vivo. The findings provide a rationale for targeting Gal-3 that may be a very promising therapeutic approach, especially for patients with relapsed/refractory AML, and may enhance the efficacy of conventional chemotherapeutic drugs and/or immune checkpoint inhibitors. Full article

Background/Objectives: ⁸⁹Zr-oxine is an ex vivo cell labeling agent that enables cells to be tracked in vivo by positron emission tomography (PET) over a period of up to two weeks. To better understand where ⁸⁹Zr-oxine binds within cellular components, factors affecting labeling and intracellular distribution of ⁸⁹Zr were examined. Methods: Mouse primary T cells, natural killer cells, dendritic cells, and monocytes, and cell lines EL4 (mouse lymphoma), DC2.4 (mouse dendritic cell), Kit225K6 (human T cell leukemia) and MC38 (mouse colon adenocarcinoma) were labeled with ⁸⁹Zr-oxine or ¹¹¹In-oxine and protein binding within the cellular compartments, the labeling thresholds, and radioactivity retention were subsequently determined. Results: Cell incorporation of ⁸⁹Zr-oxine (27.8–71.8 kBq/10⁶ cells) positively correlated with cellular size and protein mass. Most (>97%) ⁸⁹Zr was protein-bound and primarily localized in the cytoplasm, membrane, and nuclear fractions (>81%) with distribution patterns varying by cell type. By contrast, ¹¹¹In-oxine showed lower protein-binding activity of approximately 59–65%, with 62–65% of ¹¹¹In localized in the cytoplasm. Autoradiography of electrophoresed subcellular fractionated cell samples indicated stable binding by ⁸⁹Zr-oxine to proteins in all subcellular fractions but unstable protein binding by ¹¹¹In. Saturation studies showed that ⁸⁹Zr-oxine labeling was saturable, and further labeling reduced cellular retention. Biodistribution of dendritic cells labeled with either ⁸⁹Zr-oxine or ¹¹¹In-oxine indicated greater retention of ⁸⁹Zr in the labeled cells in vivo than ¹¹¹In. Conclusions: ⁸⁹Zr-oxine stably binds many intracellular proteins and shows much higher and more stable protein binding than ¹¹¹In-oxine. Intracellular protein binding of ⁸⁹Zr accounts for the ability of ⁸⁹Zr-oxine labeling to successfully track cells in vivo long-term on PET. Full article

The purpose of this study was to examine whether supplementation of ultra- and nanofiltered colostrum-based products, combined with egg yolk extract, nicotinamide mononucleotide (NMN), quercetin, alpha-ketoglutarate, white button mushroom, and celery seed extracts (the formula was patented by 4Life Research Company, USA and named as AgePro), modulate the functional activity of natural killer (NK) cells in vivo. We found that this supplement, taken orally in two capsules twice a day for 30 days, significantly enhanced the cytotoxic activity of NK cells. This was evidenced by the increased NK cell-mediated killing of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled K562 human myeloid leukemia cells. As expected, this effect was dependent on the ratio between the effector (E) (e.g., peripheral blood mononuclear cells (PBMCs)) and target (T) (e.g., K562) cells, illustrating maximal killing of K562 cells at a 50:1 E/T ratio. Of note, increased NK-mediated killing of K562 cells after taking AgePro correlated with increased perforin release, evidenced by the CD107a degranulation assay. In concordance with these findings, taking of AgePro for 1 month increased production of several cytokines and chemokines, including IL-1β, IL-1Rα, IL-6, IL-8, IL-10, IFN-γ, TNF-α, G-CSF, PDGF-AA, PDGF-AB/BB, GRO, MCP-1, MCP-3, and MIP-1α, in PBMCs co-cultured with K562 cells. Of note, increased production of the cytokines correlated with the activation state of PBMCs, as evidenced by increased expression of the surface activation markers (e.g., the interleukin-2 receptor alpha chain—CD25). A strong correlation was found between NK-based cytotoxic activity and the production of IL-1β, IL-6, TNF-α, and MIP-1α. Importantly, no increase in the aforementioned soluble factors and activation markers was detected in PBMCs cultured alone, thereby illustrating the potent immunoregulatory activity of AgePro only in the presence of the harmful target cells. Hematological parameters also remained unchanged over the entire study period. Collectively, we show herein the significant enhancement of the cytotoxic activity of NK cells against target tumor cells after taking AgePro for 1 month. Notably, this effect was observed for all age groups, including young, adult, and elderly participants. Moreover, a significant improvement in NK cytotoxic activity was also detected for participants with low basal (e.g., before taking AgePro) numbers of NK-mediated killing. The enhancement of NK-based cytotoxicity was associated with an increased release of several cytokines and chemokines involved in regulating a broad spectrum of mechanisms outside the cell-mediated cytotoxicity and killing of target cells. Of note, spontaneous activation of PBMCs, particularly NK cells, was not detected after taking AgePro. Given that spontaneous activation of autoreactive lymphocytes is a feature associated with autoimmunity and taking into account our data illustrating the AgePro-induced activation of NK cells detected only in the presence of the potentially harmful cells, we conclude that our innovative product exhibits potent immunoregulatory activity and high safety profile. Full article

Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind to the α subunit of the Na⁺/K⁺-ATPase pump and inhibit its activity. Their anticancer and antiviral activities are of interest. The α subunit of the Na⁺/K⁺-ATPase pump has four isoforms (α1–4), each with unique tissue distribution and expression pattern; their contributions to antiviral activities have not been studied. We previously reported that CGs inhibit human CMV (HCMV) in vitro but not mouse CMV (MCMV). In addition to the low affinity of mouse α1 for CGs, we hypothesized that other isoforms contribute to the anti-CMV activities of CGs. We show here that infection with HCMV significantly induced α3 in human foreskin fibroblasts, while MCMV did not induce mouse α3. Infection with guinea pig CMV (GPCMV) in GP fibroblasts also induced α3, and CGs inhibited GPCMV replication. HCMV inhibition with digitoxin reduced α3 expression. The concentration-dependent inhibition of HCMV with digitoxin analogs also correlated with α3 expression. Intriguingly, α3 was localized to the nucleus, and changes in its expression during infection and digitoxin treatment were mostly limited to the nucleus. At 4 h post-infection, α3 colocalized with immediate early 1 (IE1) and the promyelocytic leukemia protein (PML). An interaction of α3-PML-IE1 at 24 h post-infection was disrupted by digitoxin. The mRNA levels of IE1, major immediate early promoter (MIEP)-derived IE, and antiviral cytokines were reduced in infected digitoxin-treated cells. Summarized, these findings suggest a new role for α3 in the anti-HCMV activities of CGs via nuclear antiviral signaling pathways. Full article

Background: A series of spiro-fused heterocyclic compounds containing cyclopropa[a]pyrrolizidine-2,3′-oxindole and 3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole frameworks were synthesized and studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), acute T cell leukemia (Jurkat), melanoma (Sk-mel-2) and breast cancer (MCF-7) as well as mouse colon carcinoma (CT26) cell lines. Methods: Cell proliferation was evaluated in vitro by MTS assay. Confocal microscopy was used to study actin cytoskeleton structure and cell motility. Cell cycle analysis was evaluated by flow cytometry. Results: It was found that compounds 4, 8, 18 and 24 showed antiproliferative activity against the Jurkat, K-562, HeLa and Sk-mel-2 cell lines with IC₅₀ ranging from 2 to 10 μM (72 h). Evaluation of the impact on cell cycle progression showed that the tested compounds achieved significant cell-cycle perturbation with a higher accumulation of cells in the SubG1 and G0/G1 phases of the cell cycle, in comparison to the negative control. I Incubation with tested compounds led to the disappearance of stress fibers (granular actin was distributed diffusely in the cytoplasm in up to 38% of treated HeLa cells) and changes in the number of filopodia-like deformations (reduced from 93% in control cells to 64% after treatment). The impact on the Sk-mel-2 cell actin cytoskeleton structure was even greater: granular actin was distributed diffusely in the cytoplasm in up to 90% of treated cells while the number of filopodia-like deformations was reduced by up to 23%. A scratch test performed on the human melanoma cell line showed that these cells did not fill the scratched strip and lose their ability to move under treatment. Conclusions: The obtained results support the antitumor effect of the tested spiro-compounds and encourage the extension of this study in order to improve their anticancer activity as well as reduce their toxicological risks. Full article

Background: FMS-like tyrosine kinase 3 (FLT3) mutations or internal tandem duplication occur in 30% of acute myeloid leukemia (AML) cases. In these cases, FLT3 inhibitors (FLT3i) are approved for induction treatment and relapse. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the recommended post-induction therapy for suitable patients. However, the role of FLT3i therapy after alloHSCT remains unclear. Therefore, we investigated the three currently available FLT3i, gilteritinib, midostaurin, and quizartinib, in terms of their immunosuppressive effect on dendritic cells (DCs). DCs are professional antigen-presenting cells inducing T-cell responses to infectious stimuli. Highly activated DCs can also cause complications after alloHSCT, such as triggering Graft versus Host disease, a serious and potentially life-threatening complication after alloHSCT. Methods: To study the immunomodulatory effects on DCs, we differentiated murine and human DCs in the presence of FLT3i and performed immunophenotyping by flow cytometry and cytokine measurements and investigated gene and protein expression. Results: We detected a dose-dependent immunosuppressive effect of midostaurin, which decreased the expression of costimulatory markers like CD86, and found a reduced secretion of pro-inflammatory cytokines such as IL-12, TNFα, and IL-6. Mechanistically, we show that midostaurin inhibits TLR and TNF signaling and NFκB, PI3K, and MAPK pathways. The immunosuppressive effect of gilteritinib was less pronounced, while quizartinib did not show truncation of relevant signaling pathways. Conclusions: Our results suggest different immunosuppressive effects of these three FLT3i and may, therefore, provide an additional rationale for optimal maintenance therapy after alloHSCT of FLT3-positive AML patients to prevent infectious complications and GvHD mediated by DCs. Full article

Histone H1 is involved in the regulation of chromatin structure. Human somatic cells express up to seven subtypes. The variability in the proportions of somatic H1s (H1 complement) is one piece of evidence supporting their functional specificity. Alterations in the protein levels of different H1 subtypes have been observed in cancer, suggesting their potential as biomarkers and that they might play a role in disease development. We have developed a mass spectrometry-based (MS) parallel reaction monitoring (PRM) assay suitable for the quantification of H1 subtypes. Our PRM method is based on the quantification of unique peptides for each subtype, providing high specificity. Evaluation of the PRM performance on three human cell lines, HeLa, K562, and T47D, showed high reproducibility and sensitivity. Quantification values agreed with the electrophoretic and Western blot data, indicating the accuracy of the method. We used PRM to quantify the H1 complement in peripheral blood samples of healthy individuals and chronic myeloid leukemia (CML) patients. In CML, the first line of therapy is a tyrosine kinase inhibitor, imatinib. Our preliminary data revealed differences in the H1 complement in CML patients between imatinib responders and non-responders. These results support further research to determine if the H1 content or subtype composition could help predict imatinib response. Full article

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in acute myeloid leukemia (AML) are associated with poor prognosis and therapy resistance. This study aimed to demonstrate that inhibiting the deubiquitinating enzymes ubiquitin-specific peptidase 14 (USP14) and ubiquitin C-terminal hydrolase L5 (UCHL5) (USP14/UCHL5) with b-AP15 or the organogold compound auranofin (AUR) induces apoptosis in the ITD-transformed human leukemia cell line MV4-11 and mononuclear leukocytes derived from patients with FLT3-ITD-positive AML. This study included patients diagnosed with AML at Tokyo Medical and Dental University Hospital between January 2018 and July 2024. Both treatments blocked downstream FLT3 pathway events, with the effects potentiated by USP14 knockdown. Both treatments inhibited FLT3 deubiquitination via K48 and disrupted translation initiation via 4EBP1, a downstream FLT3 target. FLT3 was downregulated in the leukemic cells, with the associated activation of stress-related MAP kinase pathways and increased NF-E2-related factor 2. Furthermore, the overexpression of B-cell lymphoma-extra-large and myeloid cell leukemia-1 prevented the cell death caused by b-AP15 and AUR. These results suggest that inhibiting USP14/UCHL5, which involves multiple regulatory mechanisms, is a promising target for novel therapies for treatment-resistant FLT3-ITD-positive AML. Full article

Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs’ aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8⁺-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology. Full article

The Lucena 1 cell line, derived from the human chronic myeloid leukemia cell line K562 under selective pressure of vincristine supplementation, exhibits multidrug resistance (MDR). This study aims to explore and elucidate the underlying mechanisms driving MDR in the Lucena 1 cell line. A proteomic analysis comparing K562 and Lucena 1 revealed qualitative differences, with a focus on the ATP-dependent efflux pump, Translocase ABCB1, a key contributor to drug resistance. Tubulin analysis identified two unique isoforms, Tubulin beta 8B and alpha chain-like 3, exclusive to Lucena 1, potentially influencing resistance mechanisms. Additionally, the association of Rap1A and Krit1 in cytoskeletal regulation and the presence of STAT1, linked to the urea cycle and tumor development, offered insights into Lucena 1’s distinctive biology. The increased expression of carbonic anhydrase I suggested a role in pH regulation. The discovery of COP9, a tumor suppressor targeting p53, further highlighted the Lucena 1 complex molecular landscape. This study offers new insights into the MDR phenotype and its multifactorial consequences in cellular pathways. Thus, unraveling the mechanisms of MDR holds promise for innovating cancer models and antitumor targeted strategies, since inhibiting the P-glycoprotein (P-gp)/ABCB1 protein is not always an effective approach given the associated treatment toxicity. Full article

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS^•+ and DPPH^• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC₅₀ of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH^• assay, the IC₅₀ was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC₅₀ of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC₅₀ of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions. Full article