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Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.

Abstract Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.
PMID
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Authors

Mayor MeshTerms
Keywords

Cytotoxicity

P-glycoprotein

imatinib

multidrug resistance

polysaccharide

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28345463
OWN - NLM
STAT- MEDLINE
DA  - 20170327
DCOM- 20170407
LR  - 20170407
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 3
DP  - 2017 Mar
TI  - Computational and mechanistic studies on the effect of galactoxyloglucan:
      Imatinib nanoconjugate in imatinib resistant K562 cells.
PG  - 1010428317695946
LID - 10.1177/1010428317695946 [doi]
AB  - Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line
      treatment against chronic myelogenous leukemia. In spite of its advantageous
      viewpoints, imatinib still has genuine impediments like undesirable side effects 
      and tumor resistance during chemotherapy. Nanoparticles with sustainable release 
      profile will help in targeted delivery of anticancer drugs while minimizing
      deleterious side effects and drug resistance. The use of biopolymers like
      galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles
      could impart its use in overcoming multidrug resistance in chronic myelogenous
      leukemia patients with minimal side effects. This study involved in the synthesis
      of PST-Imatinib nanoconjugates with appreciable drug payload and excellent
      cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562)
      in comparison with free drug. The use of bioinformatics tool revealed better
      binding affinity for the drug-polysaccharide complex than the drug alone with
      three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and
      3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and
      histopathological parameters in mice upheld the security and adequacy of the
      nanoconjugate compared to free drug. Although perspective investigations are
      warranted, in a condition like drug resistance in leukemia, this nanoconjugate
      would display a productive approach in cancer therapeutics.
FAU - James, Alphy Rose
AU  - James AR
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
FAU - Unnikrishnan, B S
AU  - Unnikrishnan BS
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
FAU - Priya, R
AU  - Priya R
AD  - 2 Indian Institute of Information Technology and Management-Kerala (IIITM-K),
      Thiruvananthapuram, India.
FAU - Joseph, Manu M
AU  - Joseph MM
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
AD  - 3 Chemical Sciences & Technology Division (CSTD), CSIR - National Institute for
      Interdisciplinary Science & Technology (CSIR-NIIST), Thiruvananthapuram, India.
FAU - Manojkumar, T K
AU  - Manojkumar TK
AD  - 2 Indian Institute of Information Technology and Management-Kerala (IIITM-K),
      Thiruvananthapuram, India.
FAU - Raveendran Pillai, K
AU  - Raveendran Pillai K
AD  - 4 Clinical Laboratory Services, Regional Cancer Centre (RCC), Thiruvananthapuram,
      India.
FAU - Shiji, R
AU  - Shiji R
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
FAU - Preethi, G U
AU  - Preethi GU
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
FAU - Kusumakumary, P
AU  - Kusumakumary P
AD  - 5 Division of Pediatric Oncology, Regional Cancer Centre (RCC),
      Thiruvananthapuram, India.
FAU - Sreelekha, T T
AU  - Sreelekha TT
AD  - 1 Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research,
      Regional Cancer Centre (RCC), Thiruvananthapuram, India.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Glucans)
RN  - 0 (Nanoconjugates)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (EGFR protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
RN  - EC 5.99.1.- (DNA Topoisomerases)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cell Line, Tumor
MH  - DNA Topoisomerases/genetics
MH  - Delayed-Action Preparations/*therapeutic use
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Glucans/*therapeutic use
MH  - Humans
MH  - Imatinib Mesylate/*therapeutic use
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Nanoconjugates/*therapeutic use
MH  - Protein-Tyrosine Kinases/genetics
MH  - Receptor, Epidermal Growth Factor/genetics
MH  - Recombinant Fusion Proteins/therapeutic use
OTO - NOTNLM
OT  - Cytotoxicity
OT  - P-glycoprotein
OT  - imatinib
OT  - multidrug resistance
OT  - polysaccharide
EDAT- 2017/03/28 06:00
MHDA- 2017/04/08 06:00
CRDT- 2017/03/28 06:00
AID - 10.1177/1010428317695946 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Mar;39(3):1010428317695946. doi: 10.1177/1010428317695946.

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