PMID- 27842576
OWN - NLM
STAT- MEDLINE
DCOM- 20171003
LR  - 20191210
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 16
IP  - 1
DP  - 2016 Nov 14
TI  - Synthesis and bio-molecular study of (+)-N-Acetyl-alpha-amino acid 
      dehydroabietylamine derivative for the selective therapy of hepatocellular 
      carcinoma.
PG  - 883
LID - 883
AB  - BACKGROUND: The purpose of present work is to synthesize novel 
      (+)-Dehydroabietylamine derivatives (DAAD) using N-acetyl-alpha-amino acid conjugates 
      and determine its cytotoxic effects on hepatocellular carcinoma cells. METHODS: 
      An analytical study was conducted to explore cytotoxic activity of DAAD on 
      hepatocellular carcinoma cell lines. The cytotoxicity effect was recorded using 
      sulforhodamine B technique. Cell cycle analysis was performed using Propidium 
      Iodide (PI) staining. Based on cell morphology, anti growth activity and 
      microarray findings of DAAD2 treatment, Comet assay, Annexin V/PI staining, 
      Immunoperoxidase assay and western blots were performed accoringly. RESULTS: 
      Hep3B cells were found to be the most sensitive with IC(50) of 2.00 +/- 0.4 muM 
      against (+)-N-(N-Acetyl-L-Cysteine)-dehydroabietylamine as DAAD2. In compliance 
      to time dependent morphological changes of low cellular confluence, detachment 
      and rounding of DAAD2 treated cells; noticeable changes in G(2)/M phase were 
      recorded may be leading to cell cycle cessation. Up-regulation (5folds) of TUBA1A 
      gene in Hep3B cells was determined in microarray experiments. Apoptotic mode of 
      cell death was evaluated using standardized staining procedures including comet 
      assay and annexin V/PI staining, Immuno-peroxidase assay. Using western blotting 
      technique, caspase dependant apoptotic mode of cell death was recorded against 
      Hep3B cell line. CONCLUSION: It is concluded that a novel DAAD2 with IC(50) 
      values less than 8 muM can induce massive cell attenuation following caspase 
      dependent apoptotic cell death in Hep3B cells. Moreover, the corelation study 
      indicated that DAAD2 may have vital influence on cell prolifration properties.
FAU - Mustufa, Muhammad Ayaz
AU  - Mustufa MA
AD  - 5th Floor, PHRC Specialized Research Centre on Child Health, National Institute 
      of Child Health, Karachi, 75500, Pakistan. ayazbukero@gmail.com.
AD  - Baqai Institute of Pharmaceutical Sciences (BIPS), Baqai Medical University, 
      Karachi, 74600, Pakistan. ayazbukero@gmail.com.
AD  - Department of Molecular, Biology and Genetics, BilGen Genetics and Biotechnology 
      Center, Bilkent University, Ankara, 06800, Turkey. ayazbukero@gmail.com.
FAU - Ozen, Cigdem
AU  - Ozen C
AD  - Izmir International Biomedicine and Genome Institute, iBG-izmir, Dokuz Eylul 
      University, 35340, Balcova, Izmir, Turkey.
FAU - Hashmi, Imran Ali
AU  - Hashmi IA
AD  - Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
FAU - Aslam, Afshan
AU  - Aslam A
AD  - Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
FAU - Baig, Jameel Ahmed
AU  - Baig JA
AD  - National Center of Excellence in Analytical Chemistry, University of Sindh, 
      Jamshoro, 76080, Pakistan.
FAU - Yildiz, Gokhan
AU  - Yildiz G
AD  - Department of Medical Biology, Erzincan University Faculty of Medicine, Erzincan, 
      24100, Turkey.
FAU - Muhammad, Shoaib
AU  - Muhammad S
AD  - Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
FAU - Solangi, Imam Bakhsh
AU  - Solangi IB
AD  - Dr. M. A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, 76080, 
      Pakistan.
FAU - Ul Hasan Naqvi, Naim
AU  - Ul Hasan Naqvi N
AD  - Baqai Institute of Pharmaceutical Sciences (BIPS), Baqai Medical University, 
      Karachi, 74600, Pakistan.
FAU - Ozturk, Mehmet
AU  - Ozturk M
AD  - Izmir International Biomedicine and Genome Institute, iBG-izmir, Dokuz Eylul 
      University, 35340, Balcova, Izmir, Turkey.
FAU - Ali, Firdous Imran
AU  - Ali FI
AD  - Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan. 
      firdousilyas@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20161114
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Abietanes)
RN  - 0 (Antineoplastic Agents)
RN  - 33289O147P (dehydroabietylamine)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Abietanes/*chemical synthesis/*pharmacology
MH  - Antineoplastic Agents/*chemical synthesis/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Hepatocellular/genetics/metabolism
MH  - Caspases/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Liver Neoplasms/genetics/metabolism
PMC - PMC5109647
OTO - NOTNLM
OT  - Apoptosis
OT  - Connectivity map
OT  - Cytotoxicity
OT  - Dehydroabietylamine derivatives
OT  - Hepatocellular carcinoma
EDAT- 2016/11/16 06:00
MHDA- 2017/10/04 06:00
PMCR- 2016/11/14
CRDT- 2016/11/16 06:00
PHST- 2016/04/24 00:00 [received]
PHST- 2016/11/02 00:00 [accepted]
PHST- 2016/11/16 06:00 [entrez]
PHST- 2016/11/16 06:00 [pubmed]
PHST- 2017/10/04 06:00 [medline]
PHST- 2016/11/14 00:00 [pmc-release]
AID - 10.1186/s12885-016-2942-5 [pii]
AID - 2942 [pii]
AID - 10.1186/s12885-016-2942-5 [doi]
PST - epublish
SO  - BMC Cancer. 2016 Nov 14;16(1):883. doi: 10.1186/s12885-016-2942-5.