scholarly journals Selective Cytotoxicity of Piperine over Multidrug Resistance Leukemic Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 934
Author(s):  
Julia Quarti ◽  
Daianne N. M. Torres ◽  
Erika Ferreira ◽  
Raphael S. Vidal ◽  
Fabiana Casanova ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Black Pepper ◽  
Leukemic Cells ◽  
Glycoprotein P ◽  
Cytotoxic Effects ◽  
Collateral Sensitivity ◽  
Main Challenge ◽  
Independent Mechanism ◽  
High Level ◽  
Parp 1

Multidrug resistance (MDR) is the main challenge in the treatment of chronic myeloid leukemia (CML), and P-glycoprotein (P-gp) overexpression is an important mechanism involved in this resistance process. However, some compounds can selectively affect MDR cells, inducing collateral sensitivity (CS), which may be dependent on P-gp. The aim of this study was to investigate the effect of piperine, a phytochemical from black pepper, on CS induction in CML MDR cells, and the mechanisms involved. The results indicate that piperine induced CS, being more cytotoxic to K562-derived MDR cells (Lucena-1 and FEPS) than to K562, the parental CML cell. CS was confirmed by analysis of cell metabolic activity and viability, cell morphology and apoptosis. P-gp was partially required for CS induction. To investigate a P-gp independent mechanism, we analyzed the possibility that poly (ADP-ribose) polymerase-1 (PARP-1) could be involved in piperine cytotoxic effects. It was previously shown that only MDR FEPS cells present a high level of 24 kDa fragment of PARP-1, which could protect these cells against cell death. In the present study, piperine was able to decrease the 24 kDa fragment of PARP-1 in MDR FEPS cells. We conclude that piperine targets selectively MDR cells, inducing CS, through a mechanism that might be dependent or not on P-gp.

scholarly journals Immuno-oncology agent IPI-549 is a modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-mediated multidrug resistance (MDR) in cancer: In vitro and in vivo

2019 ◽  
Vol 442 ◽  
pp. 91-103 ◽  
Author(s):  
Albert A. De Vera ◽  
Pranav Gupta ◽  
Zining Lei ◽  
Dan Liao ◽  
Silpa Narayanan ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein

scholarly journals Collateral sensitivity as a strategy against cancer multidrug resistance

2012 ◽  
Vol 15 (1-2) ◽  
pp. 98-105 ◽  
Author(s):  
Kristen M. Pluchino ◽  
Matthew D. Hall ◽  
Andrew S. Goldsborough ◽  
Richard Callaghan ◽  
Michael M. Gottesman
Keyword(s):  
Multidrug Resistance ◽  
Collateral Sensitivity

scholarly journals Antiproliferative and Apoptosis-Inducing Activities of Benchalokawichian Remedy Against Doxorubicin-Sensitive and -Resistant Erythromyelogenous Leukemic Cells

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Wipob Suttana ◽  
Chatubhong Singharachai ◽  
Rawiwan Charoensup ◽  
Narawadee Rujanapun ◽  
Chutima Suya
Keyword(s):  
Cell Cycle ◽  
Multidrug Resistance ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Drug Resistant ◽  
Normal Cells ◽  
Root Extracts ◽  
Cycle Arrest

Chemotherapy can cause multidrug resistance in cancer cells and is cytotoxic to normal cells. Discovering natural bioactive compounds that are not cytotoxic to normal cells but inhibit proliferation and induce apoptosis in drug- sensitive and drug-resistant cancer cells could overcome these drawbacks of chemotherapy. This study investigated the antiproliferative effects of crude extracts of Benchalokawichian (BLW) remedy and its herbal components against drug-sensitive and drug-resistant cancer cells, cytotoxicity of the extracts toward normal cells, and their ability to induce apoptosis and cell cycle arrest in drug-sensitive and drug-resistant cancer cells. The extracts exhibited antiproliferative activity against doxorubicin-sensitive and doxorubicin-resistant erythromyelogenous leukemic cells (K562 and K562/adr). Tiliacora triandra root, BLW, and Harrisonia perforata root extracts displayed an IC50 of 77.00 ± 1.30, 79.33 ± 1.33, and 87.67 ± 0.67 µg/mL, respectively, against K562 cells. In contrast, Clerodendrum petasites, T. triandra, and H. perforata root extracts displayed the lowest IC50 against K562/adr cells (68.89 ± 0.75, 78.33 ± 0.69, and 86.78 ± 1.92 µg/mL, respectively). The resistance factor of the extracts was lower than that of doxorubicin, indicating that the extracts could overcome the multidrug resistance of cancer cells. Importantly, the extracts were negligibly cytotoxic to peripheral mononuclear cells, indicating minimal adverse effects in normal cells. In addition, these extracts induced apoptosis of K562 and K562/adr cells and caused cell cycle arrest at the G0/G1 phase in K562 cells. Keywords: Antiproliferative, Apoptosis, Benchalokawichian, Cell cycle, Multidrug resistance

scholarly journals Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-rui Sun ◽  
Qiu-shi Guo ◽  
Wei Zhou ◽  
Min Li
Keyword(s):  
Multidrug Resistance ◽  
Mouse Liver ◽  
Adverse Reactions ◽  
Heart Tissue ◽  
Efflux Transporters ◽  
Glycoprotein P ◽  
Chinese Herbal ◽  
Good Safety Profile ◽  
P Glycoprotein ◽  
Dioscorea Bulbifera

AbstractChinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.

scholarly journals ALGORITHM FOR TASK CONSOLIDATION IN CLOUD COMPUTING: A COMPARATIVE SURVEY

2018 ◽  
Vol 6 (5) ◽  
pp. 340-345
Author(s):  
Rajat Pugaliya ◽  
Madhu B R
Keyword(s):  
Cloud Computing ◽  
Energy Consumption ◽  
Resource Utilization ◽  
Service Provider ◽  
Virtual Machines ◽  
Cloud Service ◽  
Cloud Service Provider ◽  
Dynamic Task ◽  
Main Challenge ◽  
High Level

Cloud Computing is an emerging field in the IT industry. Cloud computing provides computing services over the Internet. Cloud Computing demand increasing drastically, which has enforced cloud service provider to ensure proper resource utilization with less cost and less energy consumption. In recent time various consolidation problems found in cloud computing like the task, VM, and server consolidation. These consolidation problems become challenging for resource utilization in cloud computing. We found in the literature review that there is a high level of coupling in resource utilization, cost, and energy consumption. The main challenge for cloud service provider is to maximize the resource utilization, reduce the cost and minimize the energy consumption. The dynamic task consolidation of virtual machines can be a way to solve the problem. This paper presents the comparative study of various task consolidation algorithms.

scholarly journals A refinement-based development of a distributed signalling system

2021 ◽  
Author(s):  
Paulius Stankaitis ◽  
Alexei Iliasov ◽  
Tsutomu Kobayashi ◽  
Yamine Aït-Ameur ◽  
Fuyuki Ishikawa ◽  
...  
Keyword(s):  
Model Verification ◽  
Modelling Language ◽  
Distributed Protocol ◽  
Rigorous Approach ◽  
Railway Systems ◽  
Main Challenge ◽  
Stepwise Development ◽  
Railway Signalling ◽  
High Level ◽  
Signalling Systems

AbstractThe decentralised railway signalling systems have a potential to increase capacity, availability and reduce maintenance costs of railway networks. However, given the safety-critical nature of railway signalling and the complexity of novel distributed signalling solutions, their safety should be guaranteed by using thorough system validation methods. To achieve such a high-level of safety assurance of these complex signalling systems, scenario-based testing methods are far from being sufficient despite that they are still widely used in the industry. Formal verification is an alternative approach which provides a rigorous approach to verifying complex systems and has been successfully used in the railway domain. Despite the successes, little work has been done in applying formal methods for distributed railway systems. In our research we are working towards a multifaceted formal development methodology of complex railway signalling systems. The methodology is based on the Event-B modelling language which provides an expressive modelling language, a stepwise development and a proof-based model verification. In this paper, we present the application of the methodology for the development and verification of a distributed protocol for reservation of railway sections. The main challenge of this work is developing a distributed protocol which ensures safety and liveness of the distributed railway system when message delays are allowed in the model.

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