PMID- 24231526
OWN - NLM
STAT- MEDLINE
DCOM- 20140311
LR  - 20161125
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 25
IP  - 2
DP  - 2014 Feb
TI  - Oxymatrine induces apoptosis in human cervical cancer cells through guanine 
      nucleotide depletion.
PG  - 161-73
LID - 10.1097/CAD.0000000000000012 [doi]
AB  - Oxymatrine is an alkaloid obtained primarily from Sophora roots and has been 
      shown to show anticancer effects in various cancers. However, the cellular and 
      molecular effects of this agent on cervical cancer have been poorly 
      characterized. Here, we investigated the antitumor effect of oxymatrine on a 
      human cervical cancer cell line (HeLa). Our results showed that application of 
      oxymatrine significantly inhibited the cell growth and tumorigenesis in a 
      dose-dependent manner and induced apoptosis through caspase-dependent pathways as 
      determined using flow cytometry and TUNEL staining analysis. To define the 
      proteins potentially related to the mechanisms of action, proteomic analysis was 
      utilized to detect proteins altered by oxymatrine. As the downregulated gene, 
      inosine monophosphate dehydrogenase type II (IMPDH2) was responsible for 
      oxymatrine-induced mitochondrial-related apoptosis. Moreover, oxymatrine depleted 
      intracellular guanosine 5'-triphosphate (GTP) levels by effective IMPDH 
      inhibition. Functional analyses further showed that oxymatrine and tiazofurin, an 
      inhibitor of IMPDH2, sensitized resistant HeLa/DDP cells to cisplatin. In 
      addition, the expression of IMPDH2 in cervical cancer was significantly higher 
      than that in the normal cervical epithelium. Taken together, these findings 
      suggest that targeting of IMPDH2 by potential pharmacological inhibitors, 
      oxymatrine in combination with chemotherapy, might be a promising means of 
      overcoming chemoresistance in cervical cancer with high IMPDH2 expression, and 
      may thus provide new insights into the mechanism of oxyamtrine-induced anticancer 
      effects.
FAU - Li, Mu
AU  - Li M
AD  - aEngineering Research Center of Biotherapy and Translational Medicine of Shaanxi 
      Province Departments of bObstetrics and Gynaecology cPathology dDisease 
      Prevention and Health Promotion eGeneral Surgery, Second Affiliated Hospital, 
      School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China.
FAU - Su, Bao-Shan
AU  - Su BS
FAU - Chang, Li-Hua
AU  - Chang LH
FAU - Gao, Qing
AU  - Gao Q
FAU - Chen, Kun-Lun
AU  - Chen KL
FAU - An, Peng
AU  - An P
FAU - Huang, Chen
AU  - Huang C
FAU - Yang, Jun
AU  - Yang J
FAU - Li, Zong-Fang
AU  - Li ZF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Alkaloids)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Quinolizines)
RN  - 85U4C366QS (oxymatrine)
RN  - EC 1.1.1.205 (IMP Dehydrogenase)
RN  - EC 1.1.1.205 (IMPDH2 protein, human)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis
MH  - Caspases/metabolism
MH  - Cell Line, Tumor/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Guanine Nucleotides/*metabolism
MH  - Humans
MH  - IMP Dehydrogenase/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mitochondria/drug effects/metabolism
MH  - Neoplasms, Squamous Cell/*drug therapy/pathology
MH  - Quinolizines/*pharmacology
MH  - Signal Transduction
MH  - Uterine Cervical Neoplasms/*drug therapy/metabolism/pathology
MH  - Xenograft Model Antitumor Assays
EDAT- 2013/11/16 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/11/16 06:00
PHST- 2013/11/16 06:00 [entrez]
PHST- 2013/11/16 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - 10.1097/CAD.0000000000000012 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2014 Feb;25(2):161-73. doi: 10.1097/CAD.0000000000000012.