PMID- 34107169
OWN - NLM
STAT- MEDLINE
DCOM- 20211123
LR  - 20211123
IS  - 1747-0285 (Electronic)
IS  - 1747-0277 (Linking)
VI  - 98
IP  - 3
DP  - 2021 Sep
TI  - Synergistic interaction of N-3-Br-benzyl-noscapine and docetaxel abrogates 
      oncogenic potential of breast cancer cells.
PG  - 466-479
LID - 10.1111/cbdd.13902 [doi]
AB  - Noscapine, an opium alkaloid, was discovered to bind tubulin, arrest dividing 
      cells at mitosis, and selectively induce apoptosis to cancer cells. 
      N-3-Br-Benzyl-Noscapine (Br-Bn-Nos), one of the derivatives of noscapine, was 
      demonstrated to have improved anticancer potential compared with noscapine. We 
      approached to evaluate the single and combined effect of Br-Bn-Nos and docetaxel 
      (DOX) based on molecular modeling and cellular study. The individual predicted 
      free energy of binding (∆G(bind,pred) ) for Br-Bn-Nos and DOX with tubulin was 
      found to be -28.89 and -36.07 kcal/mol based on molecular mechanics generalized 
      Born solvation area (MM-GBSA) as well as -26.21 and -34.65 kcal/mol based on 
      molecular mechanics Poisson Boltzmann solvation area (MM-PBSA), respectively. 
      However, the ∆G(bind,pred) of Br-Bn-Nos was significantly reduced (-33.02 and 
      -30.24 kcal/mol using MM-GBSA and MM-PBSA) in the presence of DOX on its binding 
      pocket. Parenthetically, the ∆G(bind,pred) of DOX was significantly reduced 
      (-37.17 and -32.80 kcal/mol using MM-GBSA and MM-PBSA) in the presence of 
      Br-Bn-Nos on its binding pocket. The reduced ∆G(bind,pred) in the presence of 
      Br-Bn-Nos and DOX together indicated a combination effect of both the ligands. 
      The combined interaction of both the agents onto tubulin dimmer was also 
      determined experimentally using purified tubulin, in which a combination regimen 
      of Br-Bn-Nos and DOX reduced the fluorescence intensity of tubulin to a higher 
      value (68%) compared with the single regimen. Further, isobologram analysis 
      revealed the synergistic effect of Br-Bn-Nos and DOX in antiproliferative 
      activity using MCF-7 cell line at 48 hr (sum FIC = 0.49) and at 72 hr (sum 
      FIC = 0.62). The combination dose regimen of Br-Bn-Nos and DOX blocks the cell 
      cycle progression at the G2/M phase and induces apoptosis to cancer cells more 
      effectively compared with the single regimen. Taken together, our study provides 
      compelling evidence that the anticancer potential of noscapine derivatives may be 
      substantially improved when it is used in a combined application with DOX for 
      breast cancer.
CI  - (c) 2021 John Wiley & Sons A/S.
FAU - Dash, Shruti Gamya
AU  - Dash SG
AD  - Department of Biotechnology and Bioinformatics, Centre of Excellence in Natural 
      Products and Therapeutics, Sambalpur University, Sambalpur, India.
FAU - Kantevari, Srinivas
AU  - Kantevari S
AD  - Fluoro and Agrochemicals Division, CSIR-Indian Institute of Chemical Technology, 
      Hyderabad, India.
FAU - Pandey, Swaroop Kumar
AU  - Pandey SK
AD  - Bencos Research Solutions, Mumbai, India.
FAU - Naik, Pradeep Kumar
AU  - Naik PK
AD  - Department of Biotechnology and Bioinformatics, Centre of Excellence in Natural 
      Products and Therapeutics, Sambalpur University, Sambalpur, India.
LA  - eng
GR  - Department of Science and Technology, Government of India/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210628
PL  - England
TA  - Chem Biol Drug Des
JT  - Chemical biology & drug design
JID - 101262549
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Tubulin)
RN  - 15H5577CQD (Docetaxel)
RN  - 8V32U4AOQU (Noscapine)
SB  - IM
MH  - Antineoplastic Agents/*chemistry/metabolism/pharmacology
MH  - Apoptosis/drug effects
MH  - Binding Sites
MH  - Breast Neoplasms/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Docetaxel/*chemistry/metabolism/pharmacology
MH  - Drug Synergism
MH  - Female
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Noscapine/*chemistry/metabolism/pharmacology
MH  - Thermodynamics
MH  - Tubulin/chemistry/metabolism
OTO - NOTNLM
OT  - N-3-Br benzyl Noscapine
OT  - breast cancer
OT  - combination therapy
OT  - docetaxel
OT  - isobologram
OT  - molecular docking
EDAT- 2021/06/10 06:00
MHDA- 2021/11/24 06:00
CRDT- 2021/06/09 17:38
PHST- 2021/05/12 00:00 [revised]
PHST- 2021/03/20 00:00 [received]
PHST- 2021/05/29 00:00 [accepted]
PHST- 2021/06/10 06:00 [pubmed]
PHST- 2021/11/24 06:00 [medline]
PHST- 2021/06/09 17:38 [entrez]
AID - 10.1111/cbdd.13902 [doi]
PST - ppublish
SO  - Chem Biol Drug Des. 2021 Sep;98(3):466-479. doi: 10.1111/cbdd.13902. Epub 2021 
      Jun 28.