PMID- 24638265
OWN - NLM
STAT- MEDLINE
DCOM- 20150105
LR  - 20211203
IS  - 1572-8773 (Electronic)
IS  - 0966-0844 (Linking)
VI  - 27
IP  - 3
DP  - 2014 Jun
TI  - Probing the cell death signaling pathway of HepG2 cell line induced by 
      copper-1,10-phenanthroline complex.
PG  - 445-58
LID - 10.1007/s10534-014-9710-2 [doi]
AB  - Copper-1,10-phenanthroline (phen) complex [Cu(phen)2] has been typically known as 
      DNA-cleaving agent. And now it becomes more important for developing 
      multifunctional drugs with its improved cytotoxic properties. In our study, we 
      probed the cytophysiological mechanism of Cu(phen)2. HepG2 cells were more 
      sensitive to Cu(phen)2 with an IC50 of 4.03 muM than other three kinds of cell 
      lines. After treated by Cu(phen)2, HepG2 cells had some typical morphological 
      changes which happened to its nucleus. DNA ladder's occurence and Annexin 
      V-positive increased cells indicated that Cu(phen)2 induced HepG2 cells into 
      apoptosis. Further studies showed that Cu(phen)2 treatment resulted in 
      significant G2/M phase arrest and collapse of mitochondrial membrane potential. 
      Several cell cycle-related factors were down-regulated, including Cyclin A, 
      Cyclin B1 and Cdc2. But p21 and p53 were up-regulated. DNA damage, microtubule 
      disorganization and mitotic arrest through spindle assembly checkpoint activation 
      were observed in Cu(phen)2-treated cells. The activation of caspase-3, 8 & 9 were 
      checked out. The increased-expression ratio of Bax/Bcl-2 was detected. The 
      expression levels of Bcl-xL and Bid were found to decrease. These meant that a 
      mitochondrial-related apoptosis pathway was activated in treated HepG2 cells. 
      Furthermore, some ER stress-associated signaling factors were found to be 
      up-regulated, such as Grp78, XBP-1and CHOP. Ca(2+) was also found to be released 
      from the ER lumen. Collectively, our findings demonstrate that Cu(phen)2 induces 
      apoptosis in HepG2 cells via mitotic arrest and mitochondrial- and 
      ER-stress-related signaling pathways.
FAU - Wu, Jieyuan
AU  - Wu J
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, 430072, China.
FAU - Chen, Wei
AU  - Chen W
FAU - Yin, Yan
AU  - Yin Y
FAU - Zheng, Zhongliang
AU  - Zheng Z
FAU - Zou, Guolin
AU  - Zou G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140318
PL  - Netherlands
TA  - Biometals
JT  - Biometals : an international journal on the role of metal ions in biology, 
      biochemistry, and medicine
JID - 9208478
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Phenanthrolines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (copper-1,10-phenanthroline)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - *Calcium Signaling
MH  - Cell Nucleus Shape/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - DNA Damage
MH  - Drug Screening Assays, Antitumor
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress
MH  - G2 Phase Cell Cycle Checkpoints
MH  - Hep G2 Cells
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - M Phase Cell Cycle Checkpoints
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Organometallic Compounds/*pharmacology
MH  - Phenanthrolines/*pharmacology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2014/03/19 06:00
MHDA- 2015/01/06 06:00
CRDT- 2014/03/19 06:00
PHST- 2013/12/07 00:00 [received]
PHST- 2014/01/26 00:00 [accepted]
PHST- 2014/03/19 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2015/01/06 06:00 [medline]
AID - 10.1007/s10534-014-9710-2 [doi]
PST - ppublish
SO  - Biometals. 2014 Jun;27(3):445-58. doi: 10.1007/s10534-014-9710-2. Epub 2014 Mar 
      18.