Inhibition of lipoxygenase activity and HL60 leukemic cell proliferation by ursolic acid isolated from heather flowers (Calluna vulgaris)

Author(s):  
Alain Simon ◽  
Abderrahim Najid ◽  
Albert J. Chulia ◽  
Christiane Delage ◽  
Michel Rigaud
1994 ◽  
Vol 3 (3) ◽  
pp. 181-184 ◽  
Author(s):  
D. Es-Saady ◽  
A. Najid ◽  
A. Simon ◽  
Y. Denizot ◽  
A. J. Chulia ◽  
...  

The authors have previously isolated and purified ursolic acid from heather flowers (Calluna vulgarts). This terpene was found to inhibit HL-60 leukaemic cell proliferation and arachidonic acid oxidative metabolism in various cell species. The effects of ursolic acid and its analogues on soybean 15-lipoxygenase activity and on the proliferation of a human gastric tumour cell line (HGT), have been assessed. These triterpenes inhibited soybean 15-lipoxygenase at its optimal activity (pH 9). The proliferation ofHGT was decreased in a dose-dependent manner. At 20 μM the rank order is: ursolic acid > uvaol > oleanolic acid > methyl ursolate. The carboxylic group at the C28position of ursolic acid appears to be implicated in the inhibition of both lipoxygenase activity and cell proliferation. Thus methylation of this group decreases these two inhibitory properties. Oleanolic acid, which differs by the position of one methyl group (C20instead of C19) is less inhibitory than ursolic acid. The lipophilicity of the terpene is also implicated since uvaol appears to be more inhibitory than methyl ursolate.


1994 ◽  
Vol 13 (sup1) ◽  
pp. 35-37 ◽  
Author(s):  
Christian Chabannon ◽  
Patrice Mannoni

Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Adamaki ◽  
Spiros Vlahopoulos

Acute Lymphoblastic Leukemia (ALL) is the most common neoplasm in children, but the mechanisms underlying leukemogenesis are poorly understood, despite the existence of several theories regarding the mechanics of leukemic cell proliferation. However, with the advent of new biological principles, it appears that a systems approach could be used in an effective search of global patterns in biological systems, so as to be able to model the phenomenon of proliferation and gain a better understanding of how cells may progress from a healthy to a diseased state. This chapter reviews the current knowledge on proliferation dynamics, along with a discussion of the several existing theories on leukemogenesis and their comparison with the theories governing general oncogenesis. Furthermore, the authors present some “in-house” experimental data that support the view that it is possible to model leukemic cell proliferation and explain how this has been performed in in vitro experiments.


Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1300 ◽  
Author(s):  
Songyot Anuchapreeda ◽  
Fah Chueahongthong ◽  
Natsima Viriyaadhammaa ◽  
Pawaret Panyajai ◽  
Riki Anzawa ◽  
...  

Kaffir lime (Citrus hystrix) is a plant member of family Rutaceae, and its leaves are commonly used in folk medicine. The present study explores antileukemic effects of the extracts and purified active compounds from the leaves. The antileukemic activity was investigated via inhibition of Wilms’ tumor 1 (WT1), which is a protein that involves in leukemic cell proliferation. In addition, the compounds were investigated for their effects on WT1 gene expression using real time RT-PCR and Western blotting. Cell cycle arrest and total cell number were investigated using flow cytometry and trypan blue exclusion method, respectively. The results demonstrated that the hexane fractionated extract had the greatest inhibitory effect on WT1 gene expression of many leukemic cell lines and significantly decreased WT1 protein levels of K562 cells (representative of the leukemic cells), in a dose- and time-dependent manner. Subfraction No. 9 (F9) after partial purification of hexane fractioned extract showed the highest suppression on WT1 protein and suppressed cell cycle at G2/M. The organic compounds were isolated from F9 and identified as phytol and lupeol. The bioassays confirmed antiproliferative activities of natural products phytol and lupeol. The results demonstrated anticancer activity of the isolated phytol and lupeol to decrease leukemic cell proliferation.


2020 ◽  
Vol 18 ◽  
pp. 491-503
Author(s):  
Jun-Dan Wang ◽  
Wei Zhang ◽  
Jing-Wen Zhang ◽  
Ling Zhang ◽  
Le-Xun Wang ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4402-4402
Author(s):  
Gunter Schuch ◽  
Ellen Schafer ◽  
Katharina Eggert ◽  
Sonja Loges ◽  
Manfred Jucker ◽  
...  

Abstract The tyrosine kinase pp60src is involved in several signal transduction pathways such as signalling of hematopoetic growth factors and cytokines. The viral form v-src was the first oncogene described and mutations of regulatory tyrosine residues in cellular src (c-src) have been linked to malignant transformation. However, no mutations in the gene of c-src have been described in leukemia so far, although some data of src mutations in solid tumors have been reported. The current study was undertaken to examine the role of src in acute myeloid leukemia (AML). Blood and bone marrow specimen of patients with newly diagnosed or recurrent AML treated at our institution were sampled. AML cell lines or CD34 positive cells of healthy donors served as positive and negative controls, respectively. RNA was isolated, and RT-PCR was performed using 4 different primer pairs spanning the coding region of c-src. Protein expression and phosphorylation was studied after protein extraction and Western blot analyses using src and phospho-src specific antibodies. The effect of src inhibitors PP1 and PP2 on leukemic cell proliferation was studied in human and murine cell lines. Mutational analyses of the coding region were performed using SSCP/heteroduplex and bi-directionally sequencing. In all 60 patients analyzed expression of c-src mRNA was detected by RT-PCR. Western blot analyses confirmed strong expression of src on the protein level and revealed a robust activation of the protein as determined by tyrosine phosphorylation. Inhibition of src phosphorylation by src-specific inhibitors PP1 and PP2 was detected by Western blot using an antibody specific for phospho-src. Incubation of leukemic cells with PP1 and PP2 caused significant inhibition of proliferation in a dose dependent manner. Mutational analyses as performed by SSCP/heteroduplex and bi-directionally sequencing revealed wildtype sequence in all cell lines and 60 clinical samples. In summary, pp60src is highly expressed and activated in cell lines and clinical samples of human AML. Moreover, phosphorylation of src is essential for leukemic cell proliferation. Mutations in the coding sequence of c-src causing constitutive activation could be excluded by mutational analyses of primary AML samples. These data suggest that pp60src plays a crucial role in AML and src inhibition by targeted therapy might offer a useful new approach in the treatment of AML.


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