Apoptotic mechanisms of myricitrin isolated from Madhuca longifolia leaves in HL-60 leukemia cells

2021 ◽  
Author(s):  
Monaj Kumar Sarkar ◽  
Amrita Kar ◽  
Adithyan Jayaraman ◽  
Karthi Shanmugam ◽  
Vadivel Vellingiri ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Scientific Evidence ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Potential Candidate ◽  
Caspase 9 ◽  
Madhuca Longifolia ◽  
Acute Myelogenous ◽  
Medicinal Properties

Abstract Background: Myricitrin, a naturally occurring flavonoid in Madhuca longifolia, possesses several medicinal properties. Even though our earlier work revealed its role against the proliferation of acute myelogenous leukemia cells (HL-60), its molecular mechanisms have not yet been revealed. The current study aims to explore the molecular mechanisms of myricitrin (isolated from an ethnomedicinal drug Madhuca longifolia) to induce apoptosis in HL-60 cells. Methods and Results: Treatment with IC-50 dose of myricitrin (353 µM) caused cellular shrinkage and cell wall damage in HL-60 cells compared to untreated control cells. Myricitrin treatment reduced the mitochondrial membrane potential (22.95%), increased DNA fragmentation (90.4%), inhibited the cell survival proteins (RAS, B-RAF, & BCL-2) and also induced pro-apoptotic proteins (p38, pro-caspase-3, pro-caspase-9 and caspase-3) in the HL-60 cells. Conclusions: The present study provides scientific evidence for the apoptosis caused by myricitrin in HL-60 leukemia cells. Hence, the phytochemical myricitrin could be considered as a potential candidate to develop an anticancer drug after checking its efficacy through suitable pre-clinical and clinical studies.

JS-K, a Novel Nitric Oxide (NO) Generator, Induces Cytochrome c Release and Caspase Activation in HL-60 Myeloid Leukemia Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3415-3415
Author(s):  
Paul J. Shami ◽  
Vidya Udupi ◽  
Margaret Yu ◽  
Swati Malaviya ◽  
Joseph E. Saavedra ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Dose Dependent Fashion ◽  
Acute Myelogenous ◽  
Dose Dependent

Abstract NO induces differentiation and apoptosis in Acute Myelogenous Leukemia (AML) cells. Glutathione S-Transferases (GST) play an important role in multidrug resistance and are upregulated in 90% of AML cells. We have designed a novel prodrug class that releases NO on metabolism by GST. O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antileukemic activity. We have previously shown that JS-K induces apoptosis in HL-60 cells by a caspase dependent mechanism (Molecular Cancer Therapeutics2:409-417,2003). The purpose of this study was to determine the pathway through which JS-K induces apoptosis. Western blot analysis showed that treatment of HL-60 cells with JS-K (0 – 1 μM) for 6 hours results in release of Cytochrome c from mitochondria in a dose dependent fashion. Treatment with JS-K resulted in a dose dependent activation of Caspase 9. Sixteen and 24 hours after exposure to 1 μM JS-K, Caspase 9 activity was induced by 393 ± 93% and 237 ± 13% of control, respectively (p = 0.03 at the 24 hours time point). Treatment with JS-K resulted in a dose dependent activation of Caspase 3. Twenty four hours after exposure to 1 μM JS-K, Caspase 3 activity was 208 ± 3.4 % of control (p = 0.02). Treatment with JS-K also resulted in a dose dependent activation of Caspase 8, but to a lesser extent than Caspase 9 and 3. Twenty four hours after exposure to 1 μM JS-K, Caspase 8 activity was 144 ± 5.3 % of control (p = 0.04). We conclude that JS-K activates the intrinsic pathway of apoptosis in leukemia cells by inducing the release of Cytochrome c from mitochondria. (NO1-CO-12400).

The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum

2019 ◽  
Vol 19 (9) ◽  
pp. 1114-1119 ◽  
Author(s):  
Ahmed A. Mahmoud ◽  
Wael M. El-Sayed
Keyword(s):  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Chemical Constituents ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Caspase 9 ◽  
P53 Expression ◽  
Expression And Activity

Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents. Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved. Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin. Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β−epoxy−1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression. Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

scholarly journals JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1in acute myelogenous leukemia cells

2010 ◽  
Vol 101 (3) ◽  
pp. 774-781 ◽  
Author(s):  
Nobuyuki Tajima ◽  
Kenji Fukui ◽  
Naofumi Uesato ◽  
Junji Maruhashi ◽  
Takayuki Yoshida ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Cytokine Production ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Acute Myelogenous

Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1419-1422 ◽  
Author(s):  
Giovanni Cazzaniga ◽  
Maria Grazia Dell'Oro ◽  
Cristina Mecucci ◽  
Emanuela Giarin ◽  
Riccardo Masetti ◽  
...  
Keyword(s):  
Residual Disease ◽  
Normal Karyotype ◽  
Myelogenous Leukemia ◽  
Potential Candidate ◽  
Npm1 Mutation ◽  
Reading Frame ◽  
Targeted Treatments ◽  
Acute Myelogenous ◽  
Childhood Aml ◽  
French American British

AbstractNucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumorsuppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1- mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments. (Blood. 2005;106:1419-1422)

scholarly journals Alteration of the proliferative rate of acute myelogenous leukemia cells in vivo in patients

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2600-2603 ◽  
Author(s):  
HD Preisler ◽  
A Raza ◽  
RA Larson
Keyword(s):  
Cell Cycle ◽  
Acute Myelogenous Leukemia ◽  
S Phase ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Cell Cycle Time ◽  
Proliferative Rate ◽  
Acute Myelogenous ◽  
Bioactive Agents

Abstract Ten patients with active acute myelogenous leukemia (AML) received either 13 cis retinoic acid (RA) + alpha interferon (IFN) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 3 days. Cell cycle measurements were performed before and at the conclusion of administration of the bioactive agent(s). The proliferative rate of the leukemia cells in vivo decreased in four of five patients receiving RA+IFN whereas in one patient proliferation accelerated. The proliferative rate of AML cells accelerated in three of the five patients who received rhGM-CSF and slowed in two patients. These data show that while the proliferative rate of AML cells can be altered in vivo, the effect produced by bioactive agents may be the opposite of the desired effect. Furthermore, the studies described here demonstrate the usefulness of marrow biopsies for measuring the percent S-phase cells and the importance of measuring the duration of S phase so that the effects of bioactive agents on the cell cycle time of the leukemia cells can be determined.

Somatic mutation in acute myelogenous leukemia cells imitate novel germline HLA-A allele: a case report

2014 ◽  
Vol 83 (6) ◽  
pp. 414-417 ◽  
Author(s):  
F. Mrazek ◽  
J. Onderkova ◽  
T. Szotkowski ◽  
N. Königova ◽  
Z. Ambruzova ◽  
...  
Keyword(s):  
Case Report ◽  
Somatic Mutation ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Acute Myelogenous
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