PMID- 23570653
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20220409
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 61
IP  - 17
DP  - 2013 May 1
TI  - Silibinin inhibits tumor growth through downregulation of extracellular 
      signal-regulated kinase and Akt in vitro and in vivo in human ovarian cancer 
      cells.
PG  - 4089-96
LID - 10.1021/jf400192v [doi]
AB  - Anticancer activity of silibinin, a flavonoid, has been demonstrated in various 
      cancer cell types. However, the underlying mechanisms were not elucidated in 
      human ovarian cancer cells. The present study was undertaken to examine the 
      effect of silibinin in vitro and in vivo on tumor growth in human ovarian cancer 
      cells. Silibinin decreased cell viability in a dose- and time-dependent manner. 
      Silibinin caused an increase in reactive oxygen species (ROS) generation, and the 
      silibinin-induced cell death was prevented by the antioxidant N-acetylcysteine 
      (NAC). Western blot analysis showed silibinin-induced downregulation of 
      extracellular signal-regulated kinase (ERK) and Akt. Transfection of 
      constitutively active forms of MEK and Akt prevented the silibinin-induced cell 
      death. Oral administration of silibinin in animals with subcutaneous A2780 cells 
      reduced tumor volume. Subsequent tumor tissue analysis showed that silibinin 
      treatment induced a decrease in Ki-67-positive cells, an increase in 
      transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, activation of 
      caspase-3, and inhibition of p-ERK and p-Akt. These results indicate that 
      silibinin reduces tumor growth through inhibition of ERK and Akt in human ovarian 
      cancer cells. These data suggest that silibinin may serve as a potential 
      therapeutic agent for human ovarian cancers.
FAU - Cho, Hyun Jin
AU  - Cho HJ
AD  - Department of Medicine, Graduate School of Medicine, Pusan National University , 
      Busan 602-739, Korea.
FAU - Suh, Dong Soo
AU  - Suh DS
FAU - Moon, Soo Hyeon
AU  - Moon SH
FAU - Song, Yong Jung
AU  - Song YJ
FAU - Yoon, Man Soo
AU  - Yoon MS
FAU - Park, Do Yoon
AU  - Park DY
FAU - Choi, Kyung Un
AU  - Choi KU
FAU - Kim, Yong Keun
AU  - Kim YK
FAU - Kim, Ki Hyung
AU  - Kim KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130418
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Silymarin)
RN  - 4RKY41TBTF (Silybin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/adverse effects
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Antioxidants/pharmacology
MH  - Caspase 3/genetics/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Down-Regulation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Female
MH  - Humans
MH  - Ki-67 Antigen/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovarian Neoplasms/metabolism/*pathology
MH  - Proto-Oncogene Proteins c-akt/*genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Silybin
MH  - Silymarin/*pharmacology
EDAT- 2013/04/11 06:00
MHDA- 2014/07/08 06:00
CRDT- 2013/04/11 06:00
PHST- 2013/04/11 06:00 [entrez]
PHST- 2013/04/11 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
AID - 10.1021/jf400192v [doi]
PST - ppublish
SO  - J Agric Food Chem. 2013 May 1;61(17):4089-96. doi: 10.1021/jf400192v. Epub 2013 
      Apr 18.