PMID- 22617428
OWN - NLM
STAT- MEDLINE
DCOM- 20121001
LR  - 20221207
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 262
IP  - 3
DP  - 2012 Aug 1
TI  - SL-01, an oral gemcitabine derivative, inhibited human cancer growth more 
      potently than gemcitabine.
PG  - 293-300
LID - 10.1016/j.taap.2012.05.006 [doi]
AB  - SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety 
      of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine 
      ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 
      on the growth of human cancers with gemcitabine as control. Experiments were 
      performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 
      both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the 
      growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 
      5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 
      induced the cancer cells to apoptosis showing chromatin condensation and 
      externalization of phosphatidylserine. In in vivo studies, we evaluated the 
      efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively 
      delayed the growth of NCI-H460 and HCT-116 without significant loss of body 
      weight. Molecular analysis indicated that the high efficacy of SL-01 was 
      associated with its ability to induce apoptosis as evidenced by increase of 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose 
      polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in 
      cancer cells. These biological activities of SL-01 were more potential than that 
      of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as 
      a potent oral anticancer agent that may supplant the use of gemcitabine in the 
      clinic.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Zhao, Cuirong
AU  - Zhao C
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Shandong 
      University, Jinan 250012, China.
FAU - Yue, Bin
AU  - Yue B
FAU - Liu, Huiping
AU  - Liu H
FAU - Sun, Cuicui
AU  - Sun C
FAU - Li, Wenbao
AU  - Li W
FAU - Qu, Xianjun
AU  - Qu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120519
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 
      (dodecyl-3-((1-(3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)pyrazine-2-carboxylate)
RN  - 0W860991D6 (Deoxycytidine)
RN  - EC 3.4.22.- (Caspases)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/drug therapy
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Lung Neoplasms/*drug therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Gemcitabine
EDAT- 2012/05/24 06:00
MHDA- 2012/10/02 06:00
CRDT- 2012/05/24 06:00
PHST- 2012/02/11 00:00 [received]
PHST- 2012/04/27 00:00 [revised]
PHST- 2012/05/11 00:00 [accepted]
PHST- 2012/05/24 06:00 [entrez]
PHST- 2012/05/24 06:00 [pubmed]
PHST- 2012/10/02 06:00 [medline]
AID - S0041-008X(12)00219-0 [pii]
AID - 10.1016/j.taap.2012.05.006 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2012 Aug 1;262(3):293-300. doi: 
      10.1016/j.taap.2012.05.006. Epub 2012 May 19.