PMID- 22689083
OWN - NLM
STAT- MEDLINE
DCOM- 20130204
LR  - 20211203
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 11
DP  - 2012 Nov
TI  - Wogonin induces cross-regulation between autophagy and apoptosis via a variety of 
      Akt pathway in human nasopharyngeal carcinoma cells.
PG  - 3476-85
LID - 10.1002/jcb.24224 [doi]
AB  - Autophagy as well as apoptosis is an emerging target for cancer therapy. Wogonin, 
      a flavonoid compound derived from the traditional Chinese medicine of Huang-Qin, 
      has anticancer activity in many cancer cells including human nasopharyngeal 
      carcinoma (NPC). However, the involvement of autophagy in the wogonin-induced 
      apoptosis of NPC cells was still uninvestigated. In this study, we found 
      wogonin-induced autophagy had interference on the process of apoptosis. 
      Wogonin-induced autophagy formation evidenced by LC3 I/II cleavage, acridine 
      orange (AO)-stained vacuoles and the autophagosome/autolysosome images of TEM 
      analysis. Activation of autophagy with rapamycin resulted in increased 
      wogonin-mediated autophagy via inhibition of mTOR/P70S6K pathway. The functional 
      relevance of autophagy in the antitumor activity was investigated by annexin 
      V-positive stained cells and PARP cleavage. Induction of autophagy by rapamycin 
      ameliorated the wogonin-mediated apoptosis, whereas inhibition of autophagy by 
      3-methyladenine (3-MA) or bafilomycin A1 increased the apoptotic effect. 
      Interestingly, this study also found, in addition the mTOR/P70S6K pathway, 
      wogonin also inhibited Raf/ERK pathway, a variety of Akt pathways. Inactivation 
      of PI(3) K/Akt by their inhibitors significantly induced apoptosis and markedly 
      sensitized the NPC cells to wogonin-induced apoptosis. This anticancer effect of 
      Akt was further confirmed by SH6, a specific inhibitor of Akt. Importantly, 
      inactivation of its downstream molecule ERK by PD98059, a MEK inhibitor, also 
      induced apoptosis. This study indicated wogonin-induced both autophagy and 
      apoptosis through a variety of Akt pathways and suggested modulation of autophagy 
      might provide profoundly the potential therapeutic effect.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Chow, Shu-Er
AU  - Chow SE
AD  - Center for General Studies, Chang Gung University, Taoyuan, Taiwan. 
      chowse@mail.cgu.edu.tw
FAU - Chen, Yu-Wen
AU  - Chen YW
FAU - Liang, Chi-Ang
AU  - Liang CA
FAU - Huang, Yao-Kuan
AU  - Huang YK
FAU - Wang, Jong-Shyan
AU  - Wang JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Flavanones)
RN  - 0 (Flavonoids)
RN  - 0 (Macrolides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 5142-23-4 (3-methyladenine)
RN  - 88899-55-2 (bafilomycin A1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - JAC85A2161 (Adenine)
RN  - POK93PO28W (wogonin)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Apoptosis/*drug effects/genetics
MH  - Autophagy/*drug effects/genetics
MH  - Carcinoma
MH  - Cell Line, Tumor
MH  - Drugs, Chinese Herbal/*pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Flavanones/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Macrolides/pharmacology
MH  - Nasopharyngeal Carcinoma
MH  - Nasopharyngeal Neoplasms/genetics/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - raf Kinases/genetics/metabolism
EDAT- 2012/06/13 06:00
MHDA- 2013/02/05 06:00
CRDT- 2012/06/13 06:00
PHST- 2012/06/13 06:00 [entrez]
PHST- 2012/06/13 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
AID - 10.1002/jcb.24224 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Nov;113(11):3476-85. doi: 10.1002/jcb.24224.