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Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast.

ABSTRACT: The need for new therapeutic approaches to improve the response in acute leukemia (AL), either by directing therapy or with new therapeutic alternatives, has been a research and clinical interest topic. We evaluated whether blasts from AL patients were sensitive ex vivo to the induction chemotherapy and whether the extracts of Petiveria alliacea (Anamu SC) and Caesalpinia spinosa (P2Et) modulated the sensitivity of leukemic cells to death. Bone marrow samples were taken from 26 patients with de novo AL and 6 in relapse, and the cytotoxicity of the extracts alone or in combination with the chemotherapeutic was evaluated by XTT. Patients were classified as good (GR) and bad responders (BR) according to the ex vivo test. 70.5% of the GR patients to the ex vivo test achieved postinduction remission to induction chemotherapy with a median overall survival of 12.50 months versus 7.23 months in the two groups. Furthermore, it was found that the ex vivo response to extracts and chemotherapeutics is heterogeneous and shows an exclusive pattern between the extracts, Anamu being the more effective in inducing cell death. The combination of extracts with chemotherapeutic agents showed synergistic or antagonistic effects in the patients' blasts. These results show that the ex vivo evaluation of the sensitivity to induction drugs using primary blasts from patients exhibits a correlation with the response to induction chemotherapy in patients. These analyses would allow establishing a system to predict response to treatment and determine ex vivo susceptibility to new therapies under development, among which is phytotherapeutics.

SUBMITTER: Ballesteros-Ramirez R

PROVIDER: S-EPMC7787761 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast.

Ballesteros-Ramírez Ricardo R Aldana Eliana E Herrera María Victoria MV Urueña Claudia C Rojas Laura Yinneth LY Echeverri Luis Fernando LF Costa Geison Modesti GM Quijano Sandra S Fiorentino Susana S

Evidence-based complementary and alternative medicine : eCAM 20201211

The need for new therapeutic approaches to improve the response in acute leukemia (AL), either by directing therapy or with new therapeutic alternatives, has been a research and clinical interest topic. We evaluated whether blasts from AL patients were sensitive ex vivo to the induction chemotherapy and whether the extracts of Petiveria alliacea (Anamu SC) and Caesalpinia spinosa (P2Et) modulated the sensitivity of leukemic cells to death. Bone marrow samples were taken from 26 pat ...[more]

PMID: 33488744

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Project description:Defense and protection to multiple harmful stimuli are the inflammation, when is self-amplified and uncontrolled is the basis of the pathogenesis of a wide variety of inflammatory illness. The aim of this study was to evaluate if Petiveria alliacea could attenuate inflammation in a murine model of RAW264 macrophages the involved model and its involved mechanism.The ethanol extract from P. alliacea was precipitated with water and supernatant was used for this study (PW). The anti-inflammatory effects of PW were investigated through evaluating of the production of several cytokines, chemokines, and expression of nuclear factor-kappa B (NF-κB) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Also was determined the ability to decrease the oxidative stress in RAW264.7 cells with carboxy-2',7'-dichloro-dihydro-fluorescein diacetate.PW significantly suppress the secretion of prostaglandin E2, leukotriene C4, interleukin (IL)-1 β, IL-6, IL-10, interferon gamma nitric oxide (NO), inducible NO synthase, IL-1 β, IL-4, in RAW264.7 cells in a dose-dependent manner. In addition, PW also markedly inhibited the transcriptional activity of NF-κB. PW produced significant anti-inflammatory activity through inhibiting the production of inflammatory mediators through the NF-κB inactivation in the LPS-stimulated RAW24.7 cells.PW exerts significant antioxidant and anti-inflammatory activities, and this effect can be attributed in part, to the presence of dibenzyl disulfide, dibenzyl trisulfide pinitol, coumarin, myricetin, glutamyl-S-benzyl cysteine, and petiveriins A and B.Treatment with ethanol extract from Petiveria alliacea which was previously precipitated with water and supernatant (PE) was tested in LPS-stimulated RAW264.7 cells. PE suppressed the level of oxidative stress and the induction of proinflammatory mediators, as PGE2, LTC4, IL-1 ß, IL-6, IL-10, IFN- NO, iNOS, IL-1 ß, IL-4, in RAW264.7 macrophages through NF-B inactivation. These findings suggest that P. alliacea affords promising therapeutic in inflammatory diseases. Abbreviation used: COX-2: Ciclooxigenasa 2; DCFHDA: Carboxy-2',7'-dichloro-dihydro-fluorescein diacetate; DMEM: Dulbecco's modified eagle's medium; FBS: Fetal bovine serum; HSP70: Heat shock protein; IFN-γ: Interferon gamma; IL-1 β: Interleukin 1 β, IL-6: Interleukin 6; IL-10: Interleukin 10; IL-4: Interleukin 4; iNOS: Nitric oxide synthase; KCl: Potassium chloride; LPS: Lipopolysaccharides; LTC4: leukotriene C 4; MgCl2: Magnesium chloride; MTT: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B-cells or transcriptional activity of nuclear factor-kB; NO: Nitric oxide; PBS: Phosphate-buffered saline; PGE2: Prostaglandin E2, PMSF: Phenylmethylsulfonyl fluoride; PTC: Chloroform extract from Petiveria alliacea; PE: Ethanol extract from Petiveria alliacea; PTH: Hexane extract from Petiveria alliacea; PW: Supernatant of PTE precipitated with water; RAW264.7: Cell line murine macrophages; ROS: Reactive oxygen species; TNF-α: Tumor necrosis factor.

Project description:BackgroundRepeat elements constitute a large proportion of the human genome and recent evidence indicates that repeat element expression has functional roles in both physiological and pathological states. Specifically for cancer, transcription of endogenous retrotransposons is often suppressed to attenuate an anti-tumor immune response, whereas aberrant expression of heterochromatin-derived satellite RNA has been identified as a tumor driver. These insights demonstrate separate functions for the dysregulation of distinct repeat subclasses in either the attenuation or progression of human solid tumors. For hematopoietic malignancies, such as Acute Myeloid Leukemia (AML), only very few studies on the expression/dysregulation of repeat elements were done.MethodsTo study the expression of repeat elements in AML, we performed total-RNA sequencing of healthy CD34 + cells and of leukemic blast cells from primary AML patient material. We also developed an integrative bioinformatic approach that can quantify the expression of repeat transcripts from all repeat subclasses (SINE/ALU, LINE, ERV and satellites) in relation to the expression of gene and other non-repeat transcripts (i.e. R/G ratio). This novel approach can be used as an instructive signature for repeat element expression and has been extended to the analysis of poly(A)-RNA sequencing datasets from Blueprint and TCGA consortia that together comprise 120 AML patient samples.ResultsWe identified that repeat element expression is generally down-regulated during hematopoietic differentiation and that relative changes in repeat to gene expression can stratify risk prediction of AML patients and correlate with overall survival probabilities. A high R/G ratio identifies AML patient subgroups with a favorable prognosis, whereas a low R/G ratio is prevalent in AML patient subgroups with a poor prognosis.ConclusionsWe developed an integrative bioinformatic approach that defines a general model for the analysis of repeat element dysregulation in physiological and pathological development. We find that changes in repeat to gene expression (i.e. R/G ratios) correlate with hematopoietic differentiation and can sub-stratify AML patients into low-risk and high-risk subgroups. Thus, the definition of a R/G ratio can serve as a valuable biomarker for AML and could also provide insights into differential patient response to epigenetic drug treatment.

Dataset Information

Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast.

Publications

Preferential Activity of <i>Petiveria alliacea</i> Extract on Primary Myeloid Leukemic Blast.

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