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The evidence supporting the biological plausibility of the association of permethrin and malathion with hematological cancer is limited and contradictory; thus, further studies are needed. This study aimed to investigate whether in vitro exposure to 0.1 μM permethrin and malathion at 0, 24, 48 and 72 h after cell culture initiation induced changes in the gene expression and DNA methylation in mononuclear cells from bone marrow and peripheral blood (BMMCs, PBMCs). Both pesticides induced several gene expression modifications in both tissues. Through gene ontology analysis, we found that permethrin deregulates ion channels in PBMCs and BMMCs and that malathion alters genes coding proteins with nucleic acid binding capacity, which was also observed in PBMCs exposed to permethrin. Additionally, we found that both insecticides deregulate genes coding proteins with chemotaxis functions, ion channels, and cytokines. Several genes deregulated in this study are potentially associated with cancer onset and development, and some of them have been reported to be deregulated in hematological cancer. We found that permethrin does not induce DNA hypermethylation but can induce hypomethylation, and that malathion generated both types of events. Our results suggest that these pesticides have the potential to modify gene expression through changes in promoter DNA methylation and potentially through other mechanisms that should be investigated. [ABSTRACT FROM AUTHOR]

Current antineoplastic agents present multiple disadvantages, driving an ongoing search for new and better compounds. Four lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid (2), 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), and 3α,23-dihydroxylup-20(29)-en-28-oic acid (4), previously isolated from Phoradendron wattii, were evaluated on two cell lines of chronic (K562) and acute (HL60) myeloid leukemia. Compounds 1, 2, and 4 decreased cell viability and inhibit proliferation, mainly in K562, and exhibited an apoptotic effect from 24 h of treatment. Of particular interest is compound 2, which caused arrest in active phases (G2/M) of the cell cycle, as shown by in silico study of the CDK1/Cyclin B/Csk2 complex by molecular docking. This compound [3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid] s a promising candidate for incorporation into cancer treatments and deserves further study. [ABSTRACT FROM AUTHOR]

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano–Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing. [ABSTRACT FROM AUTHOR]

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS•+) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p-coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves' extracts of A. linaria showed a high scavenging activity of DPPH• and ABTS•+ radicals (IC50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds. [ABSTRACT FROM AUTHOR]

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH • ) and 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS •+ ) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p -coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves' extracts of A. linaria showed a high scavenging activity of DPPH • and ABTS •+ radicals (IC 50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds.