Natural Products for Treatment of Chronic Myeloid Leukemia

Khajapeer, Kalubai Vari; Baskaran, Rathinasamy

doi:10.5772/66175

Cited by 4 publications

(5 citation statements)

References 240 publications

(59 reference statements)

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“…Chronic myeloid leukemia cells may also acquire resistance to imatinib by different mechanisms, such as P-gp overexpression ( 35 , 36 ). Some researchers have obtained different results with different flavonoids ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

et al. 2019

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Background:Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects.Aims:To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations.Study Design:Cell culture study.Methods:In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5‑diphenyl‑tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 μM and of imatinib from 5 to 50 μM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software.Results:In our study, the IC50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 μM, 100 μM, and >200 μM, respectively. Luteolin (100 μM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC50 concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used.Conclusion:The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

et al. 2019

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“…Several secondary metabolites from natural origin such as alkaloids, flavonoids, terpenoids, polyketides, lignans, saponins, and peptides exhibited a potent anti-CML activity (Khajapeer and Baskaran 2016).…”

Section: Introductionmentioning

confidence: 99%

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Abdelgawad

Hetta

Ibrahim

et al. 2022

Rev. Bras. Farmacogn.

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Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract

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“…It is evidenced from an earlier study that many natural products such as polyphenolic acids, flavonoids, alkaloids, terpenoids, polyketides, saponins and lignans have capacity to inhibit cell proliferation during the development of CML through the induction of apoptosis. [3] A natural phenolic compound, Hydroxychavicol (HCH) is found in Piper betle leaves with potential anti-mutagenic properties. [4] Previous studies have shown its protective efficacy against multiple cancer cells including oral cancer, [5] prostate cancer and chronic myeloid lymphoma.…”

Section: Abstract a R T I C L E I N F Omentioning

confidence: 99%

“…It was estimated approximately 90% of CML patients have shortened chromosome called "Philadelphia chromosome". [2,3]…”

Section: Introductionmentioning

confidence: 99%

Potency of Phytocompounds as Hydroxychavicol and Plumbagin in Combination to Fight Against Leukemia via Activation of MAPK-Mediated Apoptotic Pathway: An In vitro Approach

Swarnakar

Manna

Roy

et al. 2022

Int. J. Pharm. Sci. Drug Res.

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Plants provide natural molecules as an effective agent for phytomedicine. Anticancer properties of natural products are well described. Several studies on hydroxychavicol (HCH), and plumbagin (PLB), which are found in Piper betle leaf and Plumbago sp. respectively, are evidenced as anti-carcinogenic effect on chronic myeloid leukemic (CML) cells through increased reactive oxygen species (ROS). An attempt was taken to determine the efficacy of a new combination of HCH and PLB on CML cells (K562) and the mechanism of apoptosis thereon. 3-{4,5-Dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the dose for individual and combination treatments of HCH and PLB against leukemic cells, (K562). Apoptotic activity was assessed through flow cytometric analysis with annexin V-FITC/propidium iodide staining. Immunoblots were also performed on cell extracts before and after the treatments. Levels of ROS and nitric oxide (NO) in K562 cells were measured by DCF-DA and DAF-FM staining, respectively. In addition, P38 and JNK siRNA transfection were performed to assess the roles of mitogen-activated protein kinase (MAPK) pathways on apoptosis. Combination treatments of HCH (16 µM) and PLB (0.5 µM) showed synergistic effects on reducing viability and increased cellular apoptosis of K562 cells. Combined treatments showed elevated reactive oxygen species (ROS) and NO levels than individual treatments of HCH and PLB. Moreover, decreasing the ROS generations by antioxidants/ catalase reversed cell deaths and increased viability. Immunoblotting of MAPK pathways components showed reduction of pERK levels, while upregulation pJNK and pP38 levels upon HCH+PLB treatments. Furthermore, silencing of JNK and/or P38 rescued the K562 cells from deaths. The present study indicates combination treatments of HCH and PLB act as a better therapeutic against CML by promoting MAPK-mediated apoptosis via increased oxidative and nitrosative stress. This in vitro approach is the first report describing the mechanism of action of HCH/PLB to fight against Leukemia via interaction with phosphorylated P38.

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Natural Products for Treatment of Chronic Myeloid Leukemia

Cited by 4 publications

References 240 publications

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Potency of Phytocompounds as Hydroxychavicol and Plumbagin in Combination to Fight Against Leukemia via Activation of MAPK-Mediated Apoptotic Pathway: An In vitro Approach

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