PMID- 29876988
OWN - NLM
STAT- MEDLINE
DCOM- 20181031
LR  - 20191210
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 32
IP  - 10
DP  - 2018 Oct
TI  - Reactive oxygen species-mediated phosphorylation of p38 signaling is critically 
      involved in apoptotic effect of Tanshinone I in colon cancer cells.
PG  - 1975-1982
LID - 10.1002/ptr.6126 [doi]
AB  - Though Tanshinone I (Tan I), a phenolic compound from Salvia miltiorrhiza, is 
      known to have anticancer activity in several cancers, its anticancer mechanisms 
      are not fully understood in colon cancer cells. Thus, in the present study, the 
      underlying molecular mechanism of Tan I was explored in HCT116 and HT29 
      colorectal cancer cells (CRCs). Here, Tan I suppressed viability in HCT116 and 
      HT29 cells in a time- and dose-dependent manner. Also, Tan I increased the number 
      of terminal deoxynucleotide transferase-mediated dUTP nick end labeling 
      (TUNEL)-positive cells and sub-G1 population in HCT116 and HT29 cells. 
      Consistently, Tan I cleaved poly (adenosine diphosphate-ribose) polymerase (PARP) 
      and caspase-8, caspase-3, attenuated the expression of Bid and activated tBid as 
      a caspase-8 substrate and activated phosphorylation of p38 MAPK in HCT116and HT29 
      cells. Of note, Tan I generated reactive oxygen species (ROS) and conversely an 
      ROS scavenger, N-acetyl-(L) -cysteine, reversed ROS production, PARP cleavage, 
      caspase-3 activation, and p38 MAPK phosphorylation induced by Tan I in HCT116 
      cells. Furthermore, p38 MAPK inhibitor SB203580 reduced cytotoxicity, increase of 
      TUNEL-positive cells, cleavages of PARP and caspase-3 induced by Tan I in HCT116 
      cells. Overall, our findings for the first time suggest that ROS-dependent 
      activation of p38 MAPK and caspase-3 is critically involved in Tan I induced 
      apoptosis in CRCs as a potent anticancer agent.
CI  - Copyright (c) 2018 John Wiley & Sons, Ltd.
FAU - Kim, Dong Hee
AU  - Kim DH
AD  - College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
FAU - Shin, Eun Ah
AU  - Shin EA
AD  - College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
FAU - Kim, Bonglee
AU  - Kim B
AD  - College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
FAU - Shim, Bum Sang
AU  - Shim BS
AD  - College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
FAU - Kim, Sung-Hoon
AU  - Kim SH
AUID- ORCID: 0000-0003-2423-1973
AD  - College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
LA  - eng
GR  - PJ01317002/Cooperative Research Program for Agriculture Science and Technology 
      Development/
GR  - 2017R1A2A1A17069297/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20180607
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Abietanes)
RN  - 0 (Reactive Oxygen Species)
RN  - 03UUH3J385 (tanshinone)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Abietanes/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Caspase 8/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/drug therapy/*pathology
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Phosphorylation
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Salvia miltiorrhiza/chemistry
MH  - Signal Transduction/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
OTO - NOTNLM
OT  - Tanshinone I
OT  - caspase-3
OT  - colon cancer
OT  - p38
OT  - reactive oxygen species
EDAT- 2018/06/08 06:00
MHDA- 2018/11/01 06:00
CRDT- 2018/06/08 06:00
PHST- 2018/03/02 00:00 [received]
PHST- 2018/05/11 00:00 [revised]
PHST- 2018/05/15 00:00 [accepted]
PHST- 2018/06/08 06:00 [pubmed]
PHST- 2018/11/01 06:00 [medline]
PHST- 2018/06/08 06:00 [entrez]
AID - 10.1002/ptr.6126 [doi]
PST - ppublish
SO  - Phytother Res. 2018 Oct;32(10):1975-1982. doi: 10.1002/ptr.6126. Epub 2018 Jun 7.